Researchers at the MRC Prion Unit and the Department of Neurodegenerative Disease at the Institute of Neurology, University College London - in collaboration with groups from Copenhagen, Aarhus, Lund and Cambridge - have identified a gene that, when mutated, causes an early onset dementia. The discovery of the gene provides clues for the understanding of dementia and other forms of neurodegenerative disease.
The investigators studied a large family spanning 6 generations that is affected by an inherited form of early onset dementia, similar to Alzheimer's disease, called frontotemporal dementia (FTD). FTD is the second most common cause of presenile dementia. Typically the dementia strikes in the 50s and 60s and an affected parent has a 50% chance of passing on the mutated gene to their children.
FTD results in changes to behaviour and personality and causes difficulties with speech and comprehension. This genetic study of the family led to the identification of an alteration in a gene, called CHMP2b. The same gene was also found to be mutated in another FTD patient entirely unrelated to this family.
Professor John Collinge, Director of the MRC Prion Unit and Professor Elizabeth Fisher (UCL) the joint leaders of the project said: "The identification of the gene throws light on a new possible mechanism of neurodegeneration, and brings us closer to new therapies and new ways in which we can prevent the onset and progression of dementia".
The study appears online 24 July 2005 in Nature Genetics nature/naturegenetics
The MRC is a national organisation funded by the UK taxpayer. Its business is medical research aimed at improving human health; everyone stands to benefit from the outputs. The research it supports and the scientists it trains meet the needs of the health services, the pharmaceutical and other health-related industries and the academic world. MRC has funded work that has led to some of the most significant discoveries and achievements in medicine in the UK. About half of the MRC's expenditure of approximately ?500 million is invested in its 40 Institutes, Units and Centres. The remaining half goes in the form of grant support and training awards to individuals and teams in universities and medical schools. Web site at: mrc.ac.uk.
понедельник, 25 апреля 2011 г.
Lowering Blood Pressure Doesn't Prevent Cognitive Impairment, Dementia
Lowering blood pressure does not appear to prevent cognitive or dementia-related disorders, a desired effect in light of the large number of elderly adults who suffer from both cognitive impairment and hypertension.
Authors of a new systematic review analyzed three studies comprising 12,091 patients with hypertension who were treated with either medication or lifestyle strategies for at least six months while undergoing testing to assess their cognitive function. All were followed for five years.
"There is no convincing evidence that lowering blood pressure prevents the development of dementia or cognitive impairment in hypertensive patients without apparent prior cerebrovascular disease," write co-authors including A. Peter Passmore, M.D., of the department of Public Health Medicine and Primary Care at Queen's University in Belfast, Northern Ireland.
One blood-pressure medication, Nitrendipine, did appear to reduce dementia in one of the studies reviewed, but when combined with all data, this effect was not significant.
The review appears in the current issue of The Cochrane Library, a publication of The Cochrane Collaboration, an international organization that evaluates medical research. Systematic reviews draw evidence-based conclusions about medical practice after considering both the content and quality of existing medical trials on a topic.
Patients included in the study were between 60 and 89 years old with a minimum blood pressure of 160/90 and no previous cerebrovascular disease. Interventions to lower blood pressure included a variety of medications and/or lifestyle changes such as cutting salt and alcohol intake, quitting smoking and losing weight.
Vascular dementias have been linked to cardiovascular disorders, especially high blood pressure, and are often preceded by a series of small strokes. People can also suffer from a combination of vascular and Alzheimer's dementia. Hardening and narrowing of the blood vessels leading to the brain can result in gradual death of brain cells and impairments in memory, reasoning, planning and behavior.
Despite the review results, "lowering blood pressure may have beneficial effects on both atherosclerotic and blood-related mechanisms in the brain." Passmore said. "It is not clear whether it is the absolute lowering of blood pressure or the individual medications used that may affect cognition," he added.
David S. Knopman, M.D., a neurological-vascular specialist at the Mayo Clinic, says of the review, "The overall negative result of the Cochrane review can be accounted for by a number of possibilities. The studies may not have been long enough; the effects of treating hypertension probably require decades to accrue benefit. The subjects were too old and the effects of hypertension may have been sufficiently established, and damage initiated, in midlife, so that late life treatment was 'too little, too late."
He added, "Perhaps longer studies would be better, but when you deal with the elderly, there is excessive attrition from studies, which degrades the studies and makes interpretation more difficult. The problem is that the people who drop out are the sicker people, who might have been more likely to benefit from treatment."
"It is difficult to say if longer follow-up would have yielded different results," Passmore said. "The evidence from some studies suggests midlife hypertension but not late life hypertension is related to cognitive decline. It would be useful to follow younger patients for longer."
According to the National Alliance for Caregiving, the number of elderly Americans is set to double by 2050, and the number with dementia caused by Alzheimer's disease is expected to triple from current estimates of 4 million to 12 million by then.
McGuiness B, et al. The effects of blood pressure lowering on development of cognitive impairment and dementia in patients without apparent prior cerebrovascular disease. The Cochrane Database of Systematic Reviews 2006, Issue 2.
The Cochrane Collaboration is an international nonprofit, independent organization that produces and disseminates systematic reviews of health care interventions and promotes the search for evidence in the form of clinical trials and other studies of interventions. Visit cochrane for more information.
Peter Passmore
p.passmorequb.ac.uk
Center for the Advancement of Health
cfah
Authors of a new systematic review analyzed three studies comprising 12,091 patients with hypertension who were treated with either medication or lifestyle strategies for at least six months while undergoing testing to assess their cognitive function. All were followed for five years.
"There is no convincing evidence that lowering blood pressure prevents the development of dementia or cognitive impairment in hypertensive patients without apparent prior cerebrovascular disease," write co-authors including A. Peter Passmore, M.D., of the department of Public Health Medicine and Primary Care at Queen's University in Belfast, Northern Ireland.
One blood-pressure medication, Nitrendipine, did appear to reduce dementia in one of the studies reviewed, but when combined with all data, this effect was not significant.
The review appears in the current issue of The Cochrane Library, a publication of The Cochrane Collaboration, an international organization that evaluates medical research. Systematic reviews draw evidence-based conclusions about medical practice after considering both the content and quality of existing medical trials on a topic.
Patients included in the study were between 60 and 89 years old with a minimum blood pressure of 160/90 and no previous cerebrovascular disease. Interventions to lower blood pressure included a variety of medications and/or lifestyle changes such as cutting salt and alcohol intake, quitting smoking and losing weight.
Vascular dementias have been linked to cardiovascular disorders, especially high blood pressure, and are often preceded by a series of small strokes. People can also suffer from a combination of vascular and Alzheimer's dementia. Hardening and narrowing of the blood vessels leading to the brain can result in gradual death of brain cells and impairments in memory, reasoning, planning and behavior.
Despite the review results, "lowering blood pressure may have beneficial effects on both atherosclerotic and blood-related mechanisms in the brain." Passmore said. "It is not clear whether it is the absolute lowering of blood pressure or the individual medications used that may affect cognition," he added.
David S. Knopman, M.D., a neurological-vascular specialist at the Mayo Clinic, says of the review, "The overall negative result of the Cochrane review can be accounted for by a number of possibilities. The studies may not have been long enough; the effects of treating hypertension probably require decades to accrue benefit. The subjects were too old and the effects of hypertension may have been sufficiently established, and damage initiated, in midlife, so that late life treatment was 'too little, too late."
He added, "Perhaps longer studies would be better, but when you deal with the elderly, there is excessive attrition from studies, which degrades the studies and makes interpretation more difficult. The problem is that the people who drop out are the sicker people, who might have been more likely to benefit from treatment."
"It is difficult to say if longer follow-up would have yielded different results," Passmore said. "The evidence from some studies suggests midlife hypertension but not late life hypertension is related to cognitive decline. It would be useful to follow younger patients for longer."
According to the National Alliance for Caregiving, the number of elderly Americans is set to double by 2050, and the number with dementia caused by Alzheimer's disease is expected to triple from current estimates of 4 million to 12 million by then.
McGuiness B, et al. The effects of blood pressure lowering on development of cognitive impairment and dementia in patients without apparent prior cerebrovascular disease. The Cochrane Database of Systematic Reviews 2006, Issue 2.
The Cochrane Collaboration is an international nonprofit, independent organization that produces and disseminates systematic reviews of health care interventions and promotes the search for evidence in the form of clinical trials and other studies of interventions. Visit cochrane for more information.
Peter Passmore
p.passmorequb.ac.uk
Center for the Advancement of Health
cfah
Lipid Peroxides, More Sophisticated Than Their Reputation
Accumulation of lipid peroxides in the cell are associated with diseases and cellular stress. In the current issue of PNAS researchers at Helmholtz Zentrum M??nchen and the Swedish medical university Karolinska Institutet show that lipid peroxides also play an important, yet-unrecognized role in the regulation of receptor tyrosine kinases.
Neurodegenerative Diseases (DZNE) and a research group at Karolinska Institutet in Stockholm, Sweden, researchers have now discovered that lipid peroxides play a specific physiological role in the cell. Prior to this study, scientists had already established that accumulation of lipid peroxides indicate cell stress. Lipid peroxides have further been shown to be very potent inducers of cell death. The results of this study now demonstrate that chemically modified (oxidized) lipids temporarily inactivate protein tyrosine phosphatases. These in turn regulate the cellular communication of receptor tyrosine kinases (RTK). This finding is of central importance because aberrant activation of the receptor tyrosine kinases contributes to many diseases, including cancer. Until now, only hydrogen peroxide was known to oxidize and inactivate protein tyrosine phosphatases and thus to have a regulating effect on kinases.
"We were able to show that lipid peroxides are 100-1000 times more effective than hydrogen peroxide," said Dr. Marcus Conrad, lead authors of the publication, who has since moved from Helmholtz Zentrum M??nchen to the German Center for Neurodegenerative Disease. Dr. Arne Ostman and ?…sa Sandin from the Karolinska Institutet added: "It will be very interesting to see if lipid peroxides contribute to the activation of tyrosine kinases in cancer and other diseases, e.g. diabetes and Alzheimer's disease."
Background
Lipid peroxides are chemically modified lipids or fatty acids, which, among other things, indicate cellular stress. In high concentrations they can trigger cell death. Elevated concentrations of lipid peroxides are often found in patients with common diseases such as atherosclerosis, diabetes, cancer or neurodegenerative diseases including Parkinson's and Alzheimer's disease.
Receptor tyrosine kinases (RTK) and protein tyrosine phosphatases have an important function in the regulation of cell growth and division. Over-active receptor tyrosine kinases play a key role in the etiology of cancer. A frequent cause of breast cancer, for instance, is a malfunction of the receptor tyrosine kinase HER-2 (human epidermal growth factor receptor 2). In healthy tissues and cells receptor tyrosine kinases are precisely regulated by protein tyrosine phosphatases.
Source: Helmholtz Zentrum Muenchen, AlphaGalileo Foundation
Neurodegenerative Diseases (DZNE) and a research group at Karolinska Institutet in Stockholm, Sweden, researchers have now discovered that lipid peroxides play a specific physiological role in the cell. Prior to this study, scientists had already established that accumulation of lipid peroxides indicate cell stress. Lipid peroxides have further been shown to be very potent inducers of cell death. The results of this study now demonstrate that chemically modified (oxidized) lipids temporarily inactivate protein tyrosine phosphatases. These in turn regulate the cellular communication of receptor tyrosine kinases (RTK). This finding is of central importance because aberrant activation of the receptor tyrosine kinases contributes to many diseases, including cancer. Until now, only hydrogen peroxide was known to oxidize and inactivate protein tyrosine phosphatases and thus to have a regulating effect on kinases.
"We were able to show that lipid peroxides are 100-1000 times more effective than hydrogen peroxide," said Dr. Marcus Conrad, lead authors of the publication, who has since moved from Helmholtz Zentrum M??nchen to the German Center for Neurodegenerative Disease. Dr. Arne Ostman and ?…sa Sandin from the Karolinska Institutet added: "It will be very interesting to see if lipid peroxides contribute to the activation of tyrosine kinases in cancer and other diseases, e.g. diabetes and Alzheimer's disease."
Background
Lipid peroxides are chemically modified lipids or fatty acids, which, among other things, indicate cellular stress. In high concentrations they can trigger cell death. Elevated concentrations of lipid peroxides are often found in patients with common diseases such as atherosclerosis, diabetes, cancer or neurodegenerative diseases including Parkinson's and Alzheimer's disease.
Receptor tyrosine kinases (RTK) and protein tyrosine phosphatases have an important function in the regulation of cell growth and division. Over-active receptor tyrosine kinases play a key role in the etiology of cancer. A frequent cause of breast cancer, for instance, is a malfunction of the receptor tyrosine kinase HER-2 (human epidermal growth factor receptor 2). In healthy tissues and cells receptor tyrosine kinases are precisely regulated by protein tyrosine phosphatases.
Source: Helmholtz Zentrum Muenchen, AlphaGalileo Foundation
Improving Understanding Of The Brain, Learning And Memory
Neurons spoke to Dr. Joe Z. Tsien when he was a sophomore college student searching for some meaningful extracurricular activity.
He had stopped by the lab of a brain researcher at Shanghai's East China Normal University. The room was dark except for a light shining on the brain. "You could hear this pop, pop, pop, pop," says Dr. Tsien, brain scientist who recently came to the Medical College of Georgia from Boston University. "At that moment, I got interested in the brain.
"We study the questions that many people are always curious about - how the brain works, how memory works - then take it down to different levels. What is the molecular basis for the memory process? That means what genes are involved in laying down memory at a very fundamental level?" says the Georgia Research Alliance Eminent Scholar in Cognitive and Systems Neurobiology and co-director of the MCG School of Medicine's new Brain Discovery Institute. "We have been able to identify very critical memory genes and manipulate them in such a way that we can either turn them off, so the memory of mice is impaired, or enhance them."
He's talking about Doogie, a mouse that over-expresses a "smart" gene in the hippocampus, a portion of the brain critical to memory and attacked by Alzheimer's. NMDA receptors are essentially small pores on cell membranes that let ions in and increase neuronal activity and communication. Younger people have higher amounts of a NMDA subunit, NR2B, that keeps communication channels open longer so more information is shared. As people age, they switch to subunit NR2A, presumably because evolution has figured out by then we should have transmitted our genes to offspring, he says. Dr. Tsien and his colleagues made Doogie by over-expressing the NR2B gene and a conditional knockout by eliminating another NMDA receptor subunit.
Doogie was better at remembering and putting things in context, able to quickly recognize something he had seen before and move on to explore something new. He made the cover of Time magazine in 1999 and was one of Science magazines top-10 scientific breakthroughs that year. The "dumb" mouse, on the other hand, couldn't find his way out of a maze.
Dr. Tsien also has found that intelligence requires teamwork, that neurons work in cliques not only to remember specifics but also to generalize knowledge, which essentially defines intelligence.
To get a good handle on the extent of simultaneous neuronal activity, he and his former postdoctoral fellow, Dr. Longnian Lin, first developed a technique to record the activity of up to 200 mouse neurons, rather than the 20 to 30 previously possible. They then identified a small number of neurons in the hippocampus of a mouse that consistently respond to the concept of a bed or nest. Make that nest inaccessible by covering it with glass, for example, and the cells and mouse become disinterested, they showed in research published March 2007 in Proceedings of the National Academy of Sciences.
"Intelligence is really built on memory, your experiences from the past, translating that into guidelines so when you seen a new situation, you know what you need to do," says Dr. Tsien, whose collective contributions to learning and memory were featured on the July 2007 cover of Scientific American. "That helps us not only recognize our bed, for example, but to generally understand what a bed is and to know one when we see it. You check into a hotel, you know where to sleep. When you come to my office, you know where to sit. You don't sit in the floor or on my table. You sit on the chair. The chair may not be exactly like one you have seen before, but you know it's a chair. That is a basic form of intelligence."
His next project, the brain-decoding project, is about putting things in context as well, and is a major reason he came to MCG. "It's really trying to understand the essential rules of how the brain operates," says Dr. Tsien, who brought a research team of 10 with him from Boston and will recruit about eight scientists over the next two years. "It may not be a perfect analogy, but it's similar to the human genome project, where you try to assess the code. By understanding that, you form a basis to not only understand how biology works, but also how therapeutic strategies should be developed. It's a very systematic, large-scale effort to understand the brain."
One goal is understanding biology gone wrong, as it does in Alzheimer's. His lab has generated an animal model of early onset of the disease and is working to find ways to delay it. "If your brain does not kick in Alzheimer's disease until age 90, that is like a cure," he says. Another option, where Doogie may be able to help, is making better use of remaining healthy neurons in someone who already has the disease by increasing smart gene expression. "It may make those neurons work more efficiently, be better at processing information," says Dr. Tsien.
"Once you understand the rules, you can imagine that those design principles can be applied to the development of new-generation computers and robots," he says. "Once you understand the genes, the genetic codes, you can begin to identify the relationship between the mutations in those genes and disease. It gives you a better handle on how to treat it. Right now, for example, there is tremendous difficulty in developing drugs to treat schizophrenia." One problem is the lack of good animal models; it's hard to know when an animal is hallucinating or depressed. More objective measures, such as neurophysiological or other biological markers, could enable such studies, Dr. Tsien says.
He's excited that fellow brain researchers at MCG along with the system neurobiologists he's recruiting will take the lead on breaking the brain's code so that neuron speech - or silence - will be understood. "I am very excited about the leadership here and the Georgia Research Alliance is a fantastic mechanism to give researchers the opportunity to pursue really fundamental questions," says Dr. Tsien.
"Joe is an energetic scientist who already has made major contributions to our understanding of the complex brain that defines each of us," says Dr. D. Douglas Miller, dean of the MCG School of Medicine. "His work is at the core of what our new Brain Discovery Institute is about: putting together the scientific pieces of how the brain works and finding optimal ways to repair human disease when it doesn't."
"Joe Tsien's work has brought us closer to deciphering the underlying code of memory," echoes Mike Cassidy, president of the Georgia Research Alliance. "His groundbreaking research is already being applied to the development of a new generation of intelligent computers. I feel Joe's arrival foretells a very exciting future for neuroscience research in Georgia."
Dr. Tsien completed graduate school at the University of Minnesota and a Howard Hughes Medical Institute fellowship at Columbia University and Massachusetts Institute of Technology before joining the Princeton University faculty in 1997. He moved to Boston University in 2004. He is a member of the Neurobiology of Learning and Memory Study Section of the National Institutes of Health and a council member of the Society of Molecular and Cellular Cognition. His research is funded by the NIH.
Source: Toni Baker
Medical College of Georgia
He had stopped by the lab of a brain researcher at Shanghai's East China Normal University. The room was dark except for a light shining on the brain. "You could hear this pop, pop, pop, pop," says Dr. Tsien, brain scientist who recently came to the Medical College of Georgia from Boston University. "At that moment, I got interested in the brain.
"We study the questions that many people are always curious about - how the brain works, how memory works - then take it down to different levels. What is the molecular basis for the memory process? That means what genes are involved in laying down memory at a very fundamental level?" says the Georgia Research Alliance Eminent Scholar in Cognitive and Systems Neurobiology and co-director of the MCG School of Medicine's new Brain Discovery Institute. "We have been able to identify very critical memory genes and manipulate them in such a way that we can either turn them off, so the memory of mice is impaired, or enhance them."
He's talking about Doogie, a mouse that over-expresses a "smart" gene in the hippocampus, a portion of the brain critical to memory and attacked by Alzheimer's. NMDA receptors are essentially small pores on cell membranes that let ions in and increase neuronal activity and communication. Younger people have higher amounts of a NMDA subunit, NR2B, that keeps communication channels open longer so more information is shared. As people age, they switch to subunit NR2A, presumably because evolution has figured out by then we should have transmitted our genes to offspring, he says. Dr. Tsien and his colleagues made Doogie by over-expressing the NR2B gene and a conditional knockout by eliminating another NMDA receptor subunit.
Doogie was better at remembering and putting things in context, able to quickly recognize something he had seen before and move on to explore something new. He made the cover of Time magazine in 1999 and was one of Science magazines top-10 scientific breakthroughs that year. The "dumb" mouse, on the other hand, couldn't find his way out of a maze.
Dr. Tsien also has found that intelligence requires teamwork, that neurons work in cliques not only to remember specifics but also to generalize knowledge, which essentially defines intelligence.
To get a good handle on the extent of simultaneous neuronal activity, he and his former postdoctoral fellow, Dr. Longnian Lin, first developed a technique to record the activity of up to 200 mouse neurons, rather than the 20 to 30 previously possible. They then identified a small number of neurons in the hippocampus of a mouse that consistently respond to the concept of a bed or nest. Make that nest inaccessible by covering it with glass, for example, and the cells and mouse become disinterested, they showed in research published March 2007 in Proceedings of the National Academy of Sciences.
"Intelligence is really built on memory, your experiences from the past, translating that into guidelines so when you seen a new situation, you know what you need to do," says Dr. Tsien, whose collective contributions to learning and memory were featured on the July 2007 cover of Scientific American. "That helps us not only recognize our bed, for example, but to generally understand what a bed is and to know one when we see it. You check into a hotel, you know where to sleep. When you come to my office, you know where to sit. You don't sit in the floor or on my table. You sit on the chair. The chair may not be exactly like one you have seen before, but you know it's a chair. That is a basic form of intelligence."
His next project, the brain-decoding project, is about putting things in context as well, and is a major reason he came to MCG. "It's really trying to understand the essential rules of how the brain operates," says Dr. Tsien, who brought a research team of 10 with him from Boston and will recruit about eight scientists over the next two years. "It may not be a perfect analogy, but it's similar to the human genome project, where you try to assess the code. By understanding that, you form a basis to not only understand how biology works, but also how therapeutic strategies should be developed. It's a very systematic, large-scale effort to understand the brain."
One goal is understanding biology gone wrong, as it does in Alzheimer's. His lab has generated an animal model of early onset of the disease and is working to find ways to delay it. "If your brain does not kick in Alzheimer's disease until age 90, that is like a cure," he says. Another option, where Doogie may be able to help, is making better use of remaining healthy neurons in someone who already has the disease by increasing smart gene expression. "It may make those neurons work more efficiently, be better at processing information," says Dr. Tsien.
"Once you understand the rules, you can imagine that those design principles can be applied to the development of new-generation computers and robots," he says. "Once you understand the genes, the genetic codes, you can begin to identify the relationship between the mutations in those genes and disease. It gives you a better handle on how to treat it. Right now, for example, there is tremendous difficulty in developing drugs to treat schizophrenia." One problem is the lack of good animal models; it's hard to know when an animal is hallucinating or depressed. More objective measures, such as neurophysiological or other biological markers, could enable such studies, Dr. Tsien says.
He's excited that fellow brain researchers at MCG along with the system neurobiologists he's recruiting will take the lead on breaking the brain's code so that neuron speech - or silence - will be understood. "I am very excited about the leadership here and the Georgia Research Alliance is a fantastic mechanism to give researchers the opportunity to pursue really fundamental questions," says Dr. Tsien.
"Joe is an energetic scientist who already has made major contributions to our understanding of the complex brain that defines each of us," says Dr. D. Douglas Miller, dean of the MCG School of Medicine. "His work is at the core of what our new Brain Discovery Institute is about: putting together the scientific pieces of how the brain works and finding optimal ways to repair human disease when it doesn't."
"Joe Tsien's work has brought us closer to deciphering the underlying code of memory," echoes Mike Cassidy, president of the Georgia Research Alliance. "His groundbreaking research is already being applied to the development of a new generation of intelligent computers. I feel Joe's arrival foretells a very exciting future for neuroscience research in Georgia."
Dr. Tsien completed graduate school at the University of Minnesota and a Howard Hughes Medical Institute fellowship at Columbia University and Massachusetts Institute of Technology before joining the Princeton University faculty in 1997. He moved to Boston University in 2004. He is a member of the Neurobiology of Learning and Memory Study Section of the National Institutes of Health and a council member of the Society of Molecular and Cellular Cognition. His research is funded by the NIH.
Source: Toni Baker
Medical College of Georgia
David Van Day Flies In For Charity Tea Party - Alzheimer's Society
I'm a Celebrity: Get Me out of Here! star David Van Day today (20 May) swapped jungle bugs and snakes for mugs and cakes to raise vital funds and awareness for people with dementia and their carers.
The event marks the official launch of the easyJet and Alzheimer's Society charity partnership.
In his toughest challenge yet, David donned a chef's apron, hat and teapot to serve tea to thirsty easyJet cabin crew and staff in support of Alzheimer's Society. easyJet chose Alzheimer's Society as its charity of the year after a vote by 7,000 members of staff across Europe and hopes to raise ??300,000 in one year.
David Van Day says,
'It's fantastic that staff have voted for Alzheimer's Society to be their charity of the year. It is a cause that is so close to my heart as my mother has the disease.
One in three people over the age of 65 will die with dementia. It is also extremely sad for families who see their loved ones go through the traumatic experience of the condition. I hope this partnership raises enormous amounts of vital money and awareness.'
Andy Harrison, chief executive of, easyJet says,
'David Van Day donning a chef's outfit, serving tea out of a giant tea pot and a homemade cake sale; not your ordinary day in the office! But today was a fantastic start to a very important partnership. Dementia is a devastating condition that affects millions of families.
Today is just the beginning. Over the next year easyJet staff across Europe will be helping Alzheimer's Society care for people today and find a cure for tomorrow.'
Neil Hunt, chief executive of Alzheimer's Society says,
'It's been a wonderful Day for people with dementia and their carers. easyJet staff came out trumps by baking cakes and taking tea, raising vital funds and awareness.
We are hugely grateful to easyJet staff and David Van Day. Dementia is not a natural part of ageing; it is caused by diseases of the brain and has a massive impact on people's lives.'
Alzheimer's Society received 10p from every cup of tea sold. The charity will also receive donations from in-flight collections over the summer and will also be granted a percentage of proceeds from the sale of scratchcards sold on board.
Notes
- One in three people over 65 will die with dementia
- 700,000 people in the UK have a form of dementia, more than half have Alzheimer's disease. In less than 20 years nearly a million people will be living with dementia. This will soar to 1.7 million people by 2051.
- Alzheimer's Society campaigns for and champions the rights of people living with dementia and the millions of people who care for them. Alzheimer's Society works in England, Wales and Northern Ireland
- The Alzheimer's Society needs to raise money to care for people today and to find a cure for tomorrow. You can donate now by calling 0845 306 0898 or visiting alzheimers.uk
- Alzheimer's Society provides a National Dementia Helpline, the number is 0845 300 0336 or visit alzheimers.uk
Source
Alzheimer's Society
The event marks the official launch of the easyJet and Alzheimer's Society charity partnership.
In his toughest challenge yet, David donned a chef's apron, hat and teapot to serve tea to thirsty easyJet cabin crew and staff in support of Alzheimer's Society. easyJet chose Alzheimer's Society as its charity of the year after a vote by 7,000 members of staff across Europe and hopes to raise ??300,000 in one year.
David Van Day says,
'It's fantastic that staff have voted for Alzheimer's Society to be their charity of the year. It is a cause that is so close to my heart as my mother has the disease.
One in three people over the age of 65 will die with dementia. It is also extremely sad for families who see their loved ones go through the traumatic experience of the condition. I hope this partnership raises enormous amounts of vital money and awareness.'
Andy Harrison, chief executive of, easyJet says,
'David Van Day donning a chef's outfit, serving tea out of a giant tea pot and a homemade cake sale; not your ordinary day in the office! But today was a fantastic start to a very important partnership. Dementia is a devastating condition that affects millions of families.
Today is just the beginning. Over the next year easyJet staff across Europe will be helping Alzheimer's Society care for people today and find a cure for tomorrow.'
Neil Hunt, chief executive of Alzheimer's Society says,
'It's been a wonderful Day for people with dementia and their carers. easyJet staff came out trumps by baking cakes and taking tea, raising vital funds and awareness.
We are hugely grateful to easyJet staff and David Van Day. Dementia is not a natural part of ageing; it is caused by diseases of the brain and has a massive impact on people's lives.'
Alzheimer's Society received 10p from every cup of tea sold. The charity will also receive donations from in-flight collections over the summer and will also be granted a percentage of proceeds from the sale of scratchcards sold on board.
Notes
- One in three people over 65 will die with dementia
- 700,000 people in the UK have a form of dementia, more than half have Alzheimer's disease. In less than 20 years nearly a million people will be living with dementia. This will soar to 1.7 million people by 2051.
- Alzheimer's Society campaigns for and champions the rights of people living with dementia and the millions of people who care for them. Alzheimer's Society works in England, Wales and Northern Ireland
- The Alzheimer's Society needs to raise money to care for people today and to find a cure for tomorrow. You can donate now by calling 0845 306 0898 or visiting alzheimers.uk
- Alzheimer's Society provides a National Dementia Helpline, the number is 0845 300 0336 or visit alzheimers.uk
Source
Alzheimer's Society
NeuroSearch Sweden AB: Next Steps To Treat Parkinson's, Huntington's And Alzheimer's Disease
Joachim Tedroff, Head of Clinical Science at NeuroSearch Sweden AB, joined Pharma IQ to discuss Optimising Clinical Development in CNS. He discussed compound ACR16 or pridopidine, which is a generic name, that was developed in Carlsson Research about ten years ago. It belongs to a new class of
compounds called dopidines which are developed from an in vivo screening method.
Carlsson Research started with the hypothesis that there is no target but rather you have to change the way the brain works, the system, the connectivity of the various brain areas associated with Huntingdon's disease.
''What we've found out is these compounds that can modulate dopamine transmission but also strengthen glutamartology transmission could be beneficial in Huntingdon's disease and there are actually two trials now showing essentially the same thing, the Phase Three MermaiHD study and the Phase 2B study in the US called the HART study, so we are very encouraged with these results and this is actually the first time a drug ever affects key or core Huntingdon's disease symptoms'' says Tedroff.
You can download the full interview from bit.ly/e98SzD.
The interview has been conducted in relation to Pharma IQ's Optimising Clinical Development in CNS event, taking place 15 - 16 March, 2011 in London. The event is co-located with 2nd Annual Optimising Clinical Development in Oncology as a part of Clinical Trials Summit.
For more information, please visit clinicalcns, email enquireiqpc or call 44 (0) 2073679300
Source:
Pharma IQ
compounds called dopidines which are developed from an in vivo screening method.
Carlsson Research started with the hypothesis that there is no target but rather you have to change the way the brain works, the system, the connectivity of the various brain areas associated with Huntingdon's disease.
''What we've found out is these compounds that can modulate dopamine transmission but also strengthen glutamartology transmission could be beneficial in Huntingdon's disease and there are actually two trials now showing essentially the same thing, the Phase Three MermaiHD study and the Phase 2B study in the US called the HART study, so we are very encouraged with these results and this is actually the first time a drug ever affects key or core Huntingdon's disease symptoms'' says Tedroff.
You can download the full interview from bit.ly/e98SzD.
The interview has been conducted in relation to Pharma IQ's Optimising Clinical Development in CNS event, taking place 15 - 16 March, 2011 in London. The event is co-located with 2nd Annual Optimising Clinical Development in Oncology as a part of Clinical Trials Summit.
For more information, please visit clinicalcns, email enquireiqpc or call 44 (0) 2073679300
Source:
Pharma IQ
Communication Key To Dementia Care
Alzheimer's Society comment: Adults with Alzheimer's disease who are talked to like children are more resistant to care.
This is according to new research presented at the International Conference on Alzheimer's Disease (ICAD).
Good communication skills and regular interaction are vital when caring for people with dementia. This research shows that speaking to people with dementia in an adult manner not only enhances their quality of life but also improves the entire care experience.
Quality care relies on simple principles and even small changes can vastly improve quality of life for people with dementia. Alzheimer's Society research is calling for mandatory specialist dementia training to help empower staff and ensure everyone gets access to a high standard of care.
Susanne Sorensen
Head of Research
Alzheimer's Society
Reference
Kristine N. Williams. Linking communication with resistiveness to nursing care in persons with dementia.
About ICAD
The International Conference on Alzheimer's Disease (ICAD) will run from Sunday, 26 July 2008 until Wednesday 30 July 2008. Cutting edge research into dementia will be presented across the conference.
About dementia
- 1 in 3 older people will end their lives with a form of dementia.
- 700,000 people in the UK have a form of dementia, more than half have Alzheimer's disease. In less than 20 years nearly a million people will be living with dementia. This will soar to 1.7 million people by 2051. 1 in 6 people over 80 have dementia.
- Alzheimer's Society champions the rights of people living with dementia and those who care for them. Alzheimer's Society works in England, Wales and Northern Ireland.
- As a charity, Alzheimer's Society depends on the generosity of the public to help it care, research and campaign for people with dementia. You can donate now by calling 0845 306 0898 or visiting alzheimers.uk.
- Alzheimer's Society Dementia Helpline number is 0845 300 0336 or visit alzheimers.uk
Alzheimer's Society
This is according to new research presented at the International Conference on Alzheimer's Disease (ICAD).
Good communication skills and regular interaction are vital when caring for people with dementia. This research shows that speaking to people with dementia in an adult manner not only enhances their quality of life but also improves the entire care experience.
Quality care relies on simple principles and even small changes can vastly improve quality of life for people with dementia. Alzheimer's Society research is calling for mandatory specialist dementia training to help empower staff and ensure everyone gets access to a high standard of care.
Susanne Sorensen
Head of Research
Alzheimer's Society
Reference
Kristine N. Williams. Linking communication with resistiveness to nursing care in persons with dementia.
About ICAD
The International Conference on Alzheimer's Disease (ICAD) will run from Sunday, 26 July 2008 until Wednesday 30 July 2008. Cutting edge research into dementia will be presented across the conference.
About dementia
- 1 in 3 older people will end their lives with a form of dementia.
- 700,000 people in the UK have a form of dementia, more than half have Alzheimer's disease. In less than 20 years nearly a million people will be living with dementia. This will soar to 1.7 million people by 2051. 1 in 6 people over 80 have dementia.
- Alzheimer's Society champions the rights of people living with dementia and those who care for them. Alzheimer's Society works in England, Wales and Northern Ireland.
- As a charity, Alzheimer's Society depends on the generosity of the public to help it care, research and campaign for people with dementia. You can donate now by calling 0845 306 0898 or visiting alzheimers.uk.
- Alzheimer's Society Dementia Helpline number is 0845 300 0336 or visit alzheimers.uk
Alzheimer's Society
Drinking Mineral Water Could Reduce Aluminium In Alzheimer's Disease Sufferers
Scientists at Keele University in Staffordshire have found that drinking a well-known mineral water regularly could reduce the levels of aluminium in the bodies of people with Alzheimer's disease.
Ten individuals with Alzheimer's were asked to drink up to 1.5L per day of the mineral water, Volvic, for five days as part of their everyday diets. For eight out of ten it resulted in a reduction in their body burden of aluminium.
There is a link between human exposure to aluminium and the incidence of Alzheimer's disease. The objective of the research was to demonstrate a simple method whereby individuals with Alzheimer's disease (and indeed healthy individuals) could both limit their absorption of aluminium across the gut and increase their excretion of body aluminium in the urine.
Volvic is a still mineral water containing a high concentration of silicon and the research team believes that it was the silicon (the natural protector against the toxicity of aluminium) in the mineral water which helped to reduce the body burden of aluminium in the individuals with Alzheimer's disease.
Dr Chris Exley, of the Birchall Centre for Inorganic Chemistry and Materials Science, Lennard-Jones Laboratories at Keele, said: "This was a preliminary study involving only ten individuals and was carried out over only five consecutive days. We do not have any information concerning any influence of drinking the mineral water upon the disease itself only that there were no reported negative side effects."
"A future study is needed to confirm that long term drinking of a silicon-rich mineral water can reduce the body burden of aluminium in Alzheimer's disease. We shall then be able to determine if concomitant with the reduction in body aluminium there are improvements in the nature and progression of the disease."
"There is no benefit in accumulating aluminium in our bodies. Anything we can do to reduce its entry and build up in the body can only be beneficial to our health and regular drinking of silicon-rich mineral waters may be a safe and easy way to achieve the lowest possible body burden of aluminium".
In the only human trial to date to remove aluminium from the body of individuals with Alzheimer's disease, the iron chelator desferrioxamine (DFO) was successfully used to both remove aluminium from the body and slow the rate of progression of the disease. This trial, which was reported in The Lancet in 1991, has not been repeated and that may have been due to the need to inject DFO into the muscle to administer it and side-effects associated with the reaction of DFO with body iron.
Importantly, considering the earlier study using the iron chelator DFO, the new research did not influence body stores of iron and no negative side-effects of drinking the mineral water were reported.
KEELE UNIVERSITY
Keele
Staffordshire
ST5 5BG
rda28keele.ac.uk
keele.ac.uk
Ten individuals with Alzheimer's were asked to drink up to 1.5L per day of the mineral water, Volvic, for five days as part of their everyday diets. For eight out of ten it resulted in a reduction in their body burden of aluminium.
There is a link between human exposure to aluminium and the incidence of Alzheimer's disease. The objective of the research was to demonstrate a simple method whereby individuals with Alzheimer's disease (and indeed healthy individuals) could both limit their absorption of aluminium across the gut and increase their excretion of body aluminium in the urine.
Volvic is a still mineral water containing a high concentration of silicon and the research team believes that it was the silicon (the natural protector against the toxicity of aluminium) in the mineral water which helped to reduce the body burden of aluminium in the individuals with Alzheimer's disease.
Dr Chris Exley, of the Birchall Centre for Inorganic Chemistry and Materials Science, Lennard-Jones Laboratories at Keele, said: "This was a preliminary study involving only ten individuals and was carried out over only five consecutive days. We do not have any information concerning any influence of drinking the mineral water upon the disease itself only that there were no reported negative side effects."
"A future study is needed to confirm that long term drinking of a silicon-rich mineral water can reduce the body burden of aluminium in Alzheimer's disease. We shall then be able to determine if concomitant with the reduction in body aluminium there are improvements in the nature and progression of the disease."
"There is no benefit in accumulating aluminium in our bodies. Anything we can do to reduce its entry and build up in the body can only be beneficial to our health and regular drinking of silicon-rich mineral waters may be a safe and easy way to achieve the lowest possible body burden of aluminium".
In the only human trial to date to remove aluminium from the body of individuals with Alzheimer's disease, the iron chelator desferrioxamine (DFO) was successfully used to both remove aluminium from the body and slow the rate of progression of the disease. This trial, which was reported in The Lancet in 1991, has not been repeated and that may have been due to the need to inject DFO into the muscle to administer it and side-effects associated with the reaction of DFO with body iron.
Importantly, considering the earlier study using the iron chelator DFO, the new research did not influence body stores of iron and no negative side-effects of drinking the mineral water were reported.
KEELE UNIVERSITY
Keele
Staffordshire
ST5 5BG
rda28keele.ac.uk
keele.ac.uk
Biomarkers May Help Predict Risk Of Alzheimer Disease In Patients With Mild Cognitive Impairment
Several cerebrospinal fluid (CSF) biomarkers showed good accuracy in identifying patients with mild cognitive impairment who progressed to Alzheimer disease, according to a study in the July 22/29 issue of JAMA.
Alzheimer disease (AD) is the most common cause of dementia, affecting more than 15 million individuals worldwide. Because of the type of progression of the disease, there is a need for methods enabling early diagnosis. "Treatments would need to be initiated very early in the disease process, before the neurodegenerative process is too severe. Much focus has thus been directed on patients with mild cognitive impairment (MCI), which is a syndrome characterized by cognitive impairment beyond the age-adjusted norm, but not severe enough to fulfill the criteria for dementia," the authors write.
Biochemical changes in the brain are reflected in the CSF, and intense research efforts have been made to develop biomarkers for the central pathogenic processes in AD that can be used as diagnostic tools. Some studies have shown that CSF biomarkers may be useful to identify incipient (beginning) AD in patients with MCI, but most of these studies have been small and conducted at single centers, according to background information in the article.
Niklas Mattsson, M.D., of the Sahlgrenska Academy at the University of Gothenburg, M?¶lndal, Sweden, and colleagues conducted a multicenter study to assess the diagnostic accuracy of the CSF biomarkers ??-amyloid1-42 (A??42), total tau protein (T-tau), and tau phosphorylated at position threonine 181 (P-tau) in identifying incipient AD in a large group of patients with MCI. The study had two parts: a cross-sectional study involving patients with AD and controls to identify biomarker cutoff levels, followed by a prospective cohort study involving patients with MCI, conducted 1990-2007. A total of 750 individuals with MCI, 529 with AD, and 304 controls were recruited by 12 centers in Europe and the United States. Individuals with MCI were followed for at least 2 years or until symptoms had progressed to clinical dementia.
During follow-up, 271 participants with MCI were diagnosed with AD and 59 with other dementias. The researchers found that the A??42 assay in particular had considerable intersite variability. Patients who developed AD had lower median (midpoint) A??42 and higher P-tau and T-tau levels than MCI patients who did not develop AD during follow-up. Cut-offs with sensitivity (the proportion of affected individuals who have a correct positive test result for the disease that the test is intended to reveal) set at 85 percent were defined in the AD and control groups and tested in the MCI group, where the combination of A??42/P-tau ratio and T-tau identified incipient AD with a sensitivity of 83 percent and specificity (the proportion of individuals with correct negative test results for the disease the test is intended to reveal) of 72 percent.
"We determined in a large multicenter study that the CSF biomarkers A??42, T-tau, and P-tau can be used to predict with good accuracy which MCI patients will develop AD, as previously found in smaller studies. This multicenter collaboration avoids several of the risks of biases associated with single-center studies by having included substantially more patients than previous studies. Cerebrospinal fluid biomarker changes were found to be significantly associated with incipient AD. However, the considerable intercenter variations in assays and patient assessments described point to a need for standardization of sample handling as well as of clinical assessments. Although each memory clinic center followed up its cohorts prospectively and used established clinical criteria, a limitation of the present study is the lack of fully harmonized study protocols for all centers, which might account for some of the intercenter variations that we observed," the researchers write.
"Using CSF A??42, T-tau, and P-tau in memory clinics will result in some false-positive cases, as well as false-negative cases, and the biomarkers may therefore be useful primarily as screening tools, selecting individuals for a detailed further clinical follow-up. Furthermore, they may be useful in enriching study populations for clinical trials of future disease-modifying AD treatments. Until such treatments become available, however, these tests are not generally appropriate for routine clinical use because it is not currently possible to alter the development of AD."
JAMA 2009;302[4]:385-393.
Source
Journal of the American Medical Association
Alzheimer disease (AD) is the most common cause of dementia, affecting more than 15 million individuals worldwide. Because of the type of progression of the disease, there is a need for methods enabling early diagnosis. "Treatments would need to be initiated very early in the disease process, before the neurodegenerative process is too severe. Much focus has thus been directed on patients with mild cognitive impairment (MCI), which is a syndrome characterized by cognitive impairment beyond the age-adjusted norm, but not severe enough to fulfill the criteria for dementia," the authors write.
Biochemical changes in the brain are reflected in the CSF, and intense research efforts have been made to develop biomarkers for the central pathogenic processes in AD that can be used as diagnostic tools. Some studies have shown that CSF biomarkers may be useful to identify incipient (beginning) AD in patients with MCI, but most of these studies have been small and conducted at single centers, according to background information in the article.
Niklas Mattsson, M.D., of the Sahlgrenska Academy at the University of Gothenburg, M?¶lndal, Sweden, and colleagues conducted a multicenter study to assess the diagnostic accuracy of the CSF biomarkers ??-amyloid1-42 (A??42), total tau protein (T-tau), and tau phosphorylated at position threonine 181 (P-tau) in identifying incipient AD in a large group of patients with MCI. The study had two parts: a cross-sectional study involving patients with AD and controls to identify biomarker cutoff levels, followed by a prospective cohort study involving patients with MCI, conducted 1990-2007. A total of 750 individuals with MCI, 529 with AD, and 304 controls were recruited by 12 centers in Europe and the United States. Individuals with MCI were followed for at least 2 years or until symptoms had progressed to clinical dementia.
During follow-up, 271 participants with MCI were diagnosed with AD and 59 with other dementias. The researchers found that the A??42 assay in particular had considerable intersite variability. Patients who developed AD had lower median (midpoint) A??42 and higher P-tau and T-tau levels than MCI patients who did not develop AD during follow-up. Cut-offs with sensitivity (the proportion of affected individuals who have a correct positive test result for the disease that the test is intended to reveal) set at 85 percent were defined in the AD and control groups and tested in the MCI group, where the combination of A??42/P-tau ratio and T-tau identified incipient AD with a sensitivity of 83 percent and specificity (the proportion of individuals with correct negative test results for the disease the test is intended to reveal) of 72 percent.
"We determined in a large multicenter study that the CSF biomarkers A??42, T-tau, and P-tau can be used to predict with good accuracy which MCI patients will develop AD, as previously found in smaller studies. This multicenter collaboration avoids several of the risks of biases associated with single-center studies by having included substantially more patients than previous studies. Cerebrospinal fluid biomarker changes were found to be significantly associated with incipient AD. However, the considerable intercenter variations in assays and patient assessments described point to a need for standardization of sample handling as well as of clinical assessments. Although each memory clinic center followed up its cohorts prospectively and used established clinical criteria, a limitation of the present study is the lack of fully harmonized study protocols for all centers, which might account for some of the intercenter variations that we observed," the researchers write.
"Using CSF A??42, T-tau, and P-tau in memory clinics will result in some false-positive cases, as well as false-negative cases, and the biomarkers may therefore be useful primarily as screening tools, selecting individuals for a detailed further clinical follow-up. Furthermore, they may be useful in enriching study populations for clinical trials of future disease-modifying AD treatments. Until such treatments become available, however, these tests are not generally appropriate for routine clinical use because it is not currently possible to alter the development of AD."
JAMA 2009;302[4]:385-393.
Source
Journal of the American Medical Association
Alzheimer's Disease: Researchers Move Towards Prevention
A recent study directed by Mount Sinai School of Medicine identifies a faulty molecule in the brain found in cases of mild cognitive impairment (MCI). Researchers say this faulty molecule may be responsible for the progression of MCI to mild Alzheimer's disease (AD) dementia. The study, which appeared June 10th online in the journal Neurobiology of Aging, may lead to preventative treatments for AD.
An estimated 4.5 million Americans have Alzheimer's disease and presently there are no known cures or effective preventive strategies.
"Alzheimer's Disease is a growing health concern that affects millions of people, "says Giulio Maria Pasinetti, M.D., Ph.D., Professor of Psychiatry and Neuroscience, Director of the Neuroinflammation Research Center at Mount Sinai School of Medicine and lead author of the study. "We hope our research provides direction for preventative treatments to delay the onset of AD dementia by eliminating amyloid plaque-causing peptides in the brain."
People with AD exhibit elevated levels of beta-amyloid peptides that cause plaque buildup in the brain (the main characteristic of AD). In the earliest stages of Alzheimer's, beta-amyloid peptides are on the rise, especially in the two connected brain regions critical for memory functions-- the hippocampus and entorhinal cortex.
In this study, Dr. Pasinetti and colleagues at Mount Sinai School of Medicine in New York suggests one reason for that early increase of beta-amyloid peptides: an enzyme that breaks down beta-amyloid peptides, also referred to as an insulin-degrading enzyme (IDE), is not active in the brain in the cases at high-risk for developing AD. To assess possible changes in IDE during MCI, the investigators measured protein levels and enzymatic activity in postmortem brain tissue from 46 elderly subjects.
Implications
A loss of IDE activity has been previously shown to occur in severe AD dementia, and the current results raise the possibility that a deficit in degradation of amyloid peptides from IDE could raise levels of toxic beta-amyloid peptides even before AD dementia is diagnosed. If these results are confirmed, Mount Sinai researchers suggest that boosting IDE activity pharmacologically may reverse beta-amyloid peptide accumulation. This new finding may provide a pharmacological therapeutic angle to preventing AD dementia.
Dr. Pasinetti and colleagues also measured levels of beta-amyloid peptides in the entorhinal cortex and found that the amount of beta-amyloid was inversely correlated with IDE activity they measured in the hippocampus. These results support the idea that alterations in IDE might be causally related to beta-amyloid peptides accumulation, starting in the earliest stages of AD.
Mount Sinai School of Medicine
Located in Manhattan, Mount Sinai School of Medicine is internationally recognized for ground-breaking clinical and basic-science research, and innovative approaches to medical education. Through the Mount Sinai Graduate School of Biological Sciences, Mount Sinai trains biomedical researchers with an emphasis on the rapid translation of discoveries of basic research into new techniques for fighting disease. One indication of Mount Sinai's leadership in scientific investigation is its receipt during fiscal year 2005 of $174.1 million in research support from the NIH. Mount Sinai School of Medicine also is known for unique educational programs such as the Humanities in Medicine program, which creates opportunities for liberal arts students to pursue medical school, and instructional innovations like The Morchand Center, the nation's largest program teaching students and physicians with "standardized patients" to become not only highly skilled, but compassionate caregivers. Long dedicated to improving its community, the School extends its boundaries to work with East Harlem and surrounding communities to provide access to health care and educational programs to at risk populations.
Contact: Mount Sinai Press Office
The Mount Sinai Hospital / Mount Sinai School of Medicine
An estimated 4.5 million Americans have Alzheimer's disease and presently there are no known cures or effective preventive strategies.
"Alzheimer's Disease is a growing health concern that affects millions of people, "says Giulio Maria Pasinetti, M.D., Ph.D., Professor of Psychiatry and Neuroscience, Director of the Neuroinflammation Research Center at Mount Sinai School of Medicine and lead author of the study. "We hope our research provides direction for preventative treatments to delay the onset of AD dementia by eliminating amyloid plaque-causing peptides in the brain."
People with AD exhibit elevated levels of beta-amyloid peptides that cause plaque buildup in the brain (the main characteristic of AD). In the earliest stages of Alzheimer's, beta-amyloid peptides are on the rise, especially in the two connected brain regions critical for memory functions-- the hippocampus and entorhinal cortex.
In this study, Dr. Pasinetti and colleagues at Mount Sinai School of Medicine in New York suggests one reason for that early increase of beta-amyloid peptides: an enzyme that breaks down beta-amyloid peptides, also referred to as an insulin-degrading enzyme (IDE), is not active in the brain in the cases at high-risk for developing AD. To assess possible changes in IDE during MCI, the investigators measured protein levels and enzymatic activity in postmortem brain tissue from 46 elderly subjects.
Implications
A loss of IDE activity has been previously shown to occur in severe AD dementia, and the current results raise the possibility that a deficit in degradation of amyloid peptides from IDE could raise levels of toxic beta-amyloid peptides even before AD dementia is diagnosed. If these results are confirmed, Mount Sinai researchers suggest that boosting IDE activity pharmacologically may reverse beta-amyloid peptide accumulation. This new finding may provide a pharmacological therapeutic angle to preventing AD dementia.
Dr. Pasinetti and colleagues also measured levels of beta-amyloid peptides in the entorhinal cortex and found that the amount of beta-amyloid was inversely correlated with IDE activity they measured in the hippocampus. These results support the idea that alterations in IDE might be causally related to beta-amyloid peptides accumulation, starting in the earliest stages of AD.
Mount Sinai School of Medicine
Located in Manhattan, Mount Sinai School of Medicine is internationally recognized for ground-breaking clinical and basic-science research, and innovative approaches to medical education. Through the Mount Sinai Graduate School of Biological Sciences, Mount Sinai trains biomedical researchers with an emphasis on the rapid translation of discoveries of basic research into new techniques for fighting disease. One indication of Mount Sinai's leadership in scientific investigation is its receipt during fiscal year 2005 of $174.1 million in research support from the NIH. Mount Sinai School of Medicine also is known for unique educational programs such as the Humanities in Medicine program, which creates opportunities for liberal arts students to pursue medical school, and instructional innovations like The Morchand Center, the nation's largest program teaching students and physicians with "standardized patients" to become not only highly skilled, but compassionate caregivers. Long dedicated to improving its community, the School extends its boundaries to work with East Harlem and surrounding communities to provide access to health care and educational programs to at risk populations.
Contact: Mount Sinai Press Office
The Mount Sinai Hospital / Mount Sinai School of Medicine
New Compound Stops Brain Cell Degeneration In Alzheimer's Disease
Drug discovery researchers at Northwestern University have developed a novel orally administered compound specifically targeted to suppress brain cell inflammation and neuron loss associated with Alzheimer's disease.
The compound is also rapidly absorbed by the brain and is non-toxic - important considerations for a central nervous system drug that might need to be taken for extended periods.
As described in the Jan. 11 issue of the Journal of Neuroscience, the compound, called MW01-5-188WH, selectively inhibits production of pro-inflammatory proteins called cytokines by glia, important cells of the central nervous system that normally help the body mount a response, but are overactivated in certain neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, stroke and traumatic brain injury.
The compound was designed and synthesized in the laboratory of D. Martin Watterson at Northwestern University Feinberg School of Medicine, using a synthetic chemistry platform developed in his lab by researchers at the Northwestern University Center for Drug Discovery and Chemical Biology (CDDCB) for the rapid discovery of new potential therapeutic compounds.
Watterson is co-director of the CDDCB, the J.G. Searle Professor of Molecular Biology and Biochemistry and professor of molecular pharmacology and biological chemistry at the Feinberg School.
The efficacy and safety of the compound in an animal model of Alzheimer's disease was evaluated in collaboration with Linda J. Van Eldik, co-director of the CDDCB and professor of cell and molecular biology at Feinberg.
Besides providing a lead compound for drug development, the study has important implications for drug discovery in neurodegenerative diseases in general because it provides proof of concept that targeting over-production of cytokines by activated glia is a viable approach that has the potential to modulate disease onset and progression, the researchers said.
Decline of cognitive functions linked to the part of the brain called the hippocampus is a clinical hallmark of Alzheimer's disease. The report demonstrates that targeting excessive glial activation can suppress brain inflammation and neuron dysfunction in the hippocampus and protect against cognitive decline in an animal model.
Neuron dysfunction can lead to further glia activation and contribute to further exacerbation of the disease process. The Northwestern researchers found that 188WH and related compounds slowed or reversed the progression of the neuroinflammatory cascade and reduced human amyloid beta-induced glia activation in a mouse specially designed to develop many of the signs of Alzheimer's disease, including neuroinflammation, neuronal and synaptic degeneration and behavioral deficits.
The compound also restored normal levels of markers of synaptic dysfunction in the hippocampus, the area of the brain that helps regulate memory and is gradually destroyed in neurodegenerative diseases such as Alzheimer's. Treatment with the compound also attenuated Alzheimer's-like behavioral deficits in the mice that are due to injury to the hippocampus.
While previous research by the authors and many other investigators in the field has linked plaques, tangles and neuronal injury to synaptic dysfunction and cognitive decline, the direct linkage of glia to these processes and their potential as a selective target for new therapies has not previously been implicated so directly.
There are three key aspects of the report, Watterson said.
"First, a novel compound for development into a new class of Alzheimer's disease therapeutics that target disease has been described. Second, an innovative approach was used for the rapid and cost-effective discovery of orally bioavailable, safe and efficacious compounds, and this approach can be extended to other disease areas," Watterson said.
"Third, the design, synthesis and in vivo analyses were carried out by a new generation of young scientists trained in our educational program to instruct the next generation of interdisciplinary scientists," Watterson said.
Northwestern University patented the compound designated 188WH and has exclusively licensed the patent rights to NeuroMedix, Inc., for clinical development.
Co-authors with Watterson and Van Eldik on this report were senior staff biologist Ling Guao; post-doctoral trainees Hantamalala Ralay Ranaivo and Wenhui Hu; and pre-doctoral trainees Jeffrey M. Craft and Laura K. Wing, Center for Drug Discovery and Chemical Biology, Northwestern University.
This research was supported in part by funds from the Institute for the Study of Aging; from the National Institutes of Health (AG013939; NS047586; AG021184; N0S46942; and AG000260); from the PhRMA Foundation; and from NeuroMedix, Inc.
Elizabeth Crown
e-crownnorthwestern
Northwestern University
northwestern
The compound is also rapidly absorbed by the brain and is non-toxic - important considerations for a central nervous system drug that might need to be taken for extended periods.
As described in the Jan. 11 issue of the Journal of Neuroscience, the compound, called MW01-5-188WH, selectively inhibits production of pro-inflammatory proteins called cytokines by glia, important cells of the central nervous system that normally help the body mount a response, but are overactivated in certain neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, stroke and traumatic brain injury.
The compound was designed and synthesized in the laboratory of D. Martin Watterson at Northwestern University Feinberg School of Medicine, using a synthetic chemistry platform developed in his lab by researchers at the Northwestern University Center for Drug Discovery and Chemical Biology (CDDCB) for the rapid discovery of new potential therapeutic compounds.
Watterson is co-director of the CDDCB, the J.G. Searle Professor of Molecular Biology and Biochemistry and professor of molecular pharmacology and biological chemistry at the Feinberg School.
The efficacy and safety of the compound in an animal model of Alzheimer's disease was evaluated in collaboration with Linda J. Van Eldik, co-director of the CDDCB and professor of cell and molecular biology at Feinberg.
Besides providing a lead compound for drug development, the study has important implications for drug discovery in neurodegenerative diseases in general because it provides proof of concept that targeting over-production of cytokines by activated glia is a viable approach that has the potential to modulate disease onset and progression, the researchers said.
Decline of cognitive functions linked to the part of the brain called the hippocampus is a clinical hallmark of Alzheimer's disease. The report demonstrates that targeting excessive glial activation can suppress brain inflammation and neuron dysfunction in the hippocampus and protect against cognitive decline in an animal model.
Neuron dysfunction can lead to further glia activation and contribute to further exacerbation of the disease process. The Northwestern researchers found that 188WH and related compounds slowed or reversed the progression of the neuroinflammatory cascade and reduced human amyloid beta-induced glia activation in a mouse specially designed to develop many of the signs of Alzheimer's disease, including neuroinflammation, neuronal and synaptic degeneration and behavioral deficits.
The compound also restored normal levels of markers of synaptic dysfunction in the hippocampus, the area of the brain that helps regulate memory and is gradually destroyed in neurodegenerative diseases such as Alzheimer's. Treatment with the compound also attenuated Alzheimer's-like behavioral deficits in the mice that are due to injury to the hippocampus.
While previous research by the authors and many other investigators in the field has linked plaques, tangles and neuronal injury to synaptic dysfunction and cognitive decline, the direct linkage of glia to these processes and their potential as a selective target for new therapies has not previously been implicated so directly.
There are three key aspects of the report, Watterson said.
"First, a novel compound for development into a new class of Alzheimer's disease therapeutics that target disease has been described. Second, an innovative approach was used for the rapid and cost-effective discovery of orally bioavailable, safe and efficacious compounds, and this approach can be extended to other disease areas," Watterson said.
"Third, the design, synthesis and in vivo analyses were carried out by a new generation of young scientists trained in our educational program to instruct the next generation of interdisciplinary scientists," Watterson said.
Northwestern University patented the compound designated 188WH and has exclusively licensed the patent rights to NeuroMedix, Inc., for clinical development.
Co-authors with Watterson and Van Eldik on this report were senior staff biologist Ling Guao; post-doctoral trainees Hantamalala Ralay Ranaivo and Wenhui Hu; and pre-doctoral trainees Jeffrey M. Craft and Laura K. Wing, Center for Drug Discovery and Chemical Biology, Northwestern University.
This research was supported in part by funds from the Institute for the Study of Aging; from the National Institutes of Health (AG013939; NS047586; AG021184; N0S46942; and AG000260); from the PhRMA Foundation; and from NeuroMedix, Inc.
Elizabeth Crown
e-crownnorthwestern
Northwestern University
northwestern
Potential Underlying Cause For Dementia After Cancer Treatment Suggested By Study
Researchers at Wake Forest University School of Medicine have identified changes in brain chemistry that may be associated with the dementia that many cancer patients develop after whole-brain radiation treatment.
"By identifying exactly how radiation causes these side effects, our hope is that we can find a way to prevent or reverse them," said Lei Shi, M.D., Ph.D., lead author and a research fellow.
Whole-brain radiation is widely used to treat recurrent brain tumors as well as to prevent breast cancer, lung cancer and malignant melanoma from spreading to the brain. About 200,000 people receive the treatments annually. Starting at about a year post-treatment, up to one-half develop progressive memory problems.
Researchers don't know precisely how radiation injures the brain, but suspect it causes changes in the brain's communication system. To test this theory, Shi and colleagues evaluated rats that had been treated with radiation and developed learning and memory impairments.
At the annual meeting of the Radiation Research Society in Philadelphia, 6-Nov-2006, the researchers said they found changes in brain receptors for glutamate - a neurotransmitter, or molecule that carries signals between nerve cells. They said the receptors change in composition as a result of whole-brain irradiation and that the changes seem to be associated with cognitive deficits.
These findings are significant because they may lay the groundwork for developing new therapies to prevent or reverse these potentially devastating impairments induced by whole-brain irradiation.
"There is a growing concern about the cognitive consequences of whole-brain radiation," said Judy Brunso-Bechtold, Ph.D., a professor of neurobiology and anatomy and senior researcher. "Our findings suggest that very subtle changes may be critical and that glutamate receptors may be one of those changes."
The researchers focused on middle-age rats because middle-age adults are most prone to the cancers that require whole-brain irradiation treatment. Half of the rats received doses of whole-brain radiation similar to what humans receive. The other half received "sham" treatments that involved no radiation. One year later, researchers tested the rats' learning and memory using a water maze.
The rats that had received radiation performed significantly worse than the untreated animals. Additional experiments were conducted to determine if these deficits were associated with cell-to-cell communication in the hippocampus, a region of the brain associated with learning and memory.
The scientists specifically looked at glutamate receptors that lie on cell membranes. There are several different subtypes of the receptors that differ in the types of brain chemicals that most readily bind to them. They found that the composition of these subtypes was different in the animals receiving whole-brain irradiation.
"This shift in composition could impair synaptic communication and lead to the spatial learning and memory deficits measured in the treated rats," said Shi.
Next, the researchers will see if the chemical changes also extend to the synapses themselves. They also want to focus on why some animals - and people - experience cognitive deficits while others don't. Eventually, they hope to test drug therapies that may prevent the effects.
Shi received the 2006 Marie Curie Award from the Radiation Research Society for the research.
The research is supported by a recently funded grant from the National Institutes of Health and is part of a broad collaboration among researchers led by Michael Robbins, Ph.D., in the Department of Radiation Oncology. Other co-researchers were Michelle Adams, Ph.D., Michelle Nicolle, Ph.D., William Sonntag, Ph.D., and Kenneth Wheeler, Ph.D., all from Wake Forest.
Wake Forest University Baptist Medical Center is an academic health system comprised of North Carolina Baptist Hospital and Wake Forest University Health Sciences, which operates the university's School of Medicine. U.S. News & World Report ranks Wake Forest University School of Medicine 18th in family medicine, 20th in geriatrics, 25th in primary care and 41st in research among the nation's medical schools. It ranks 35th in research funding by the National Institutes of Health. Almost 150 members of the medical school faculty are listed in Best Doctors in America.
Contact: Karen Richardson
Wake Forest University Baptist Medical Center
"By identifying exactly how radiation causes these side effects, our hope is that we can find a way to prevent or reverse them," said Lei Shi, M.D., Ph.D., lead author and a research fellow.
Whole-brain radiation is widely used to treat recurrent brain tumors as well as to prevent breast cancer, lung cancer and malignant melanoma from spreading to the brain. About 200,000 people receive the treatments annually. Starting at about a year post-treatment, up to one-half develop progressive memory problems.
Researchers don't know precisely how radiation injures the brain, but suspect it causes changes in the brain's communication system. To test this theory, Shi and colleagues evaluated rats that had been treated with radiation and developed learning and memory impairments.
At the annual meeting of the Radiation Research Society in Philadelphia, 6-Nov-2006, the researchers said they found changes in brain receptors for glutamate - a neurotransmitter, or molecule that carries signals between nerve cells. They said the receptors change in composition as a result of whole-brain irradiation and that the changes seem to be associated with cognitive deficits.
These findings are significant because they may lay the groundwork for developing new therapies to prevent or reverse these potentially devastating impairments induced by whole-brain irradiation.
"There is a growing concern about the cognitive consequences of whole-brain radiation," said Judy Brunso-Bechtold, Ph.D., a professor of neurobiology and anatomy and senior researcher. "Our findings suggest that very subtle changes may be critical and that glutamate receptors may be one of those changes."
The researchers focused on middle-age rats because middle-age adults are most prone to the cancers that require whole-brain irradiation treatment. Half of the rats received doses of whole-brain radiation similar to what humans receive. The other half received "sham" treatments that involved no radiation. One year later, researchers tested the rats' learning and memory using a water maze.
The rats that had received radiation performed significantly worse than the untreated animals. Additional experiments were conducted to determine if these deficits were associated with cell-to-cell communication in the hippocampus, a region of the brain associated with learning and memory.
The scientists specifically looked at glutamate receptors that lie on cell membranes. There are several different subtypes of the receptors that differ in the types of brain chemicals that most readily bind to them. They found that the composition of these subtypes was different in the animals receiving whole-brain irradiation.
"This shift in composition could impair synaptic communication and lead to the spatial learning and memory deficits measured in the treated rats," said Shi.
Next, the researchers will see if the chemical changes also extend to the synapses themselves. They also want to focus on why some animals - and people - experience cognitive deficits while others don't. Eventually, they hope to test drug therapies that may prevent the effects.
Shi received the 2006 Marie Curie Award from the Radiation Research Society for the research.
The research is supported by a recently funded grant from the National Institutes of Health and is part of a broad collaboration among researchers led by Michael Robbins, Ph.D., in the Department of Radiation Oncology. Other co-researchers were Michelle Adams, Ph.D., Michelle Nicolle, Ph.D., William Sonntag, Ph.D., and Kenneth Wheeler, Ph.D., all from Wake Forest.
Wake Forest University Baptist Medical Center is an academic health system comprised of North Carolina Baptist Hospital and Wake Forest University Health Sciences, which operates the university's School of Medicine. U.S. News & World Report ranks Wake Forest University School of Medicine 18th in family medicine, 20th in geriatrics, 25th in primary care and 41st in research among the nation's medical schools. It ranks 35th in research funding by the National Institutes of Health. Almost 150 members of the medical school faculty are listed in Best Doctors in America.
Contact: Karen Richardson
Wake Forest University Baptist Medical Center
Dementia In NHS Operating Framework Critical, UK
A shake-up of the health system was confirmed in the NHS Operating Framework, published this week.
Alongside the framework, PCTs learned they will receive ??89 billion for frontline services.
Alzheimer's Society welcomed a commitment from David Nicholson, Chief Executive of the NHS who reaffirmed the NHS commitment to strengthen dementia services. Alzheimer's Society warned that dementia could bankrupt the NHS unless urgent action is taken. Dementia costs the UK ??20 billion more than heart disease, stroke and cancer combined. This cost will triple within a generation.
Alzheimer's Society comment:
'The NHS is facing its biggest shakeup in modern history and funding cuts will mean tough times ahead. The prioritisation this framework gives to dementia is therefore critical. With the number of people affected by dementia set to soar to a million in less than 15 years, dementia has the potential to bankrupt the NHS.'
Andrew Chidgey
Head of Policy and Public Affairs
Source:
Alzheimer's Society
Alongside the framework, PCTs learned they will receive ??89 billion for frontline services.
Alzheimer's Society welcomed a commitment from David Nicholson, Chief Executive of the NHS who reaffirmed the NHS commitment to strengthen dementia services. Alzheimer's Society warned that dementia could bankrupt the NHS unless urgent action is taken. Dementia costs the UK ??20 billion more than heart disease, stroke and cancer combined. This cost will triple within a generation.
Alzheimer's Society comment:
'The NHS is facing its biggest shakeup in modern history and funding cuts will mean tough times ahead. The prioritisation this framework gives to dementia is therefore critical. With the number of people affected by dementia set to soar to a million in less than 15 years, dementia has the potential to bankrupt the NHS.'
Andrew Chidgey
Head of Policy and Public Affairs
Source:
Alzheimer's Society
Forest And Merz Announce FDA Approval Of Namenda XR For The Treatment Of Moderate To Severe Dementia Of The Alzheimer's Type
Forest Laboratories, Inc. (NYSE: FRX) and Merz Pharmaceuticals GmbH announced that Namenda XR(TM) (memantine hydrochloride) was approved by the U.S. Food and Drug Administration for the treatment of moderate to severe dementia of the Alzheimer's type. Namenda XR is a 28 mg once-daily extended-release formulation of NAMENDA. The safety and efficacy of Namenda XR were established in a randomized, double-blind, placebo-controlled trial of 677 outpatients already taking a cholinesterase inhibitor. The results indicate that patients treated with Namenda XR experienced statistically significant benefits in cognition and clinical global status compared to placebo.
Namenda XR will be covered by U.S. Patent No. 5,061,703, which is listed in the Orange Book for Namenda and expires in April 2015. In addition, Forest owns pending patent applications related to Namenda XR. The companies are determining the appropriate commercialization strategy and market timing to ensure a successful franchise.
About Namenda XR
Namenda XR(memantine HCl) extended release capsules are a 28mg once-daily formulation of Namenda approved for the treatment of moderate to severe dementia of the Alzheimer's type. Namenda, a twice daily immediate release formulation, was approved in October 2003. Namenda XR has a mechanism of action that focuses on the glutamate pathway, a target for the treatment of Alzheimer's disease.
Important Safety Information
Contraindications
- Namenda XR is contraindicated in patients with known hypersensitivity to memantine hydrochloride or to any excipients used in the formulation.
Precautions
- Caregivers should be instructed in the recommended administration (once per day) and about dose escalation (minimum interval of one week between dose increases).
- Namenda XR has not been systematically evaluated in patients with a seizure disorder.
- Namenda XR should be used with caution under conditions that raise urine pH (including alterations by diet, drugs and the clinical state of the patient). Alkaline urine conditions may decrease the urinary elimination of memantine, resulting in increased plasma levels.
- A dosage reduction is recommended in patients with severe renal impairment.
- Namenda XR should be administered with caution to patients with severe hepatic impairment.
Adverse Reactions
- In clinical trials, the most common adverse events occurring in at least 5% of patients treated with Namenda XR and at a greater frequency than placebo-treated patients were headache (6% vs 5%), diarrhea (5% vs 4%), and dizziness (5% vs 1%).
Source:
Merz Pharmaceuticals
Forest Laboratories
View drug information on Namenda.
Namenda XR will be covered by U.S. Patent No. 5,061,703, which is listed in the Orange Book for Namenda and expires in April 2015. In addition, Forest owns pending patent applications related to Namenda XR. The companies are determining the appropriate commercialization strategy and market timing to ensure a successful franchise.
About Namenda XR
Namenda XR(memantine HCl) extended release capsules are a 28mg once-daily formulation of Namenda approved for the treatment of moderate to severe dementia of the Alzheimer's type. Namenda, a twice daily immediate release formulation, was approved in October 2003. Namenda XR has a mechanism of action that focuses on the glutamate pathway, a target for the treatment of Alzheimer's disease.
Important Safety Information
Contraindications
- Namenda XR is contraindicated in patients with known hypersensitivity to memantine hydrochloride or to any excipients used in the formulation.
Precautions
- Caregivers should be instructed in the recommended administration (once per day) and about dose escalation (minimum interval of one week between dose increases).
- Namenda XR has not been systematically evaluated in patients with a seizure disorder.
- Namenda XR should be used with caution under conditions that raise urine pH (including alterations by diet, drugs and the clinical state of the patient). Alkaline urine conditions may decrease the urinary elimination of memantine, resulting in increased plasma levels.
- A dosage reduction is recommended in patients with severe renal impairment.
- Namenda XR should be administered with caution to patients with severe hepatic impairment.
Adverse Reactions
- In clinical trials, the most common adverse events occurring in at least 5% of patients treated with Namenda XR and at a greater frequency than placebo-treated patients were headache (6% vs 5%), diarrhea (5% vs 4%), and dizziness (5% vs 1%).
Source:
Merz Pharmaceuticals
Forest Laboratories
View drug information on Namenda.
Early Defects In Intracellular Physical Transport System May Be Driving Force Behind Severe Neuronal Dysfunction
Stem cell derived neurons may allow scientists to determine whether breakdowns in the transport of proteins, lipids and other materials within cells trigger the neuronal death and neurodegeneration that characterize Alzheimer's disease (AD) and the rarer but always fatal neurological disorder, Niemann-Pick Type C (NPC), according to a presentation that Lawrence B. Goldstein, Ph.D., of the University of California, San Diego, School of Medicine and Howard Hughes Medical Institute (HHMI) gave at the American Society for Cell Biology (ASCB) 49th Annual Meeting, Dec. 5-9, 2009 in San Diego.
In research using fruit flies, mice and human cell cultures as lab models, Goldstein pioneered the study of how early defects in the intracellular physical transport system may be the driving force behind severe neuronal dysfunction.
Using human embryonic stem cells (hESCs), Goldstein and his team have produced human neurons in which the NPC gene is switched off, providing the first close look at cellular transport in a human neuron lacking normal function of the gene.
With induced pluripotent stem cells (IPS), Goldstein has derived human neurons representing the genetic "familial" form of AD as well as the far more common "sporadic" AD.
By comparing the biochemical and cellular makeup of these two types of stem cell derived neurons, Goldstein hopes to reveal how their known genetic differences affect their transport of vital cellular cargoes and other cellular behaviors.
Such research "may yield an understanding of what components of sporadic disease are defined by genetic characteristics," said Goldstein, professor in the Department of Cellular & Molecular Medicine, an HHMI investigator and director of UC San Diego's Stem Cell Program.
AD is now the seventh leading cause of death in the U.S., according to the National Centers for Health Statistics. The National Niemann-Pick Disease Foundation reports that children born with NPC rarely survive beyond the age of 20.
Lawrence S.B. Goldstein, Ph.D. presented "Human pluripotent stem cell models of Alzheimer's Disease and Niemann-Pick Type C," Minisymposium 28: ES Cells, iPS Cells, and Germ Cells, Abstract #2381.
Source: Cathy Yarbrough
American Society for Cell Biology
In research using fruit flies, mice and human cell cultures as lab models, Goldstein pioneered the study of how early defects in the intracellular physical transport system may be the driving force behind severe neuronal dysfunction.
Using human embryonic stem cells (hESCs), Goldstein and his team have produced human neurons in which the NPC gene is switched off, providing the first close look at cellular transport in a human neuron lacking normal function of the gene.
With induced pluripotent stem cells (IPS), Goldstein has derived human neurons representing the genetic "familial" form of AD as well as the far more common "sporadic" AD.
By comparing the biochemical and cellular makeup of these two types of stem cell derived neurons, Goldstein hopes to reveal how their known genetic differences affect their transport of vital cellular cargoes and other cellular behaviors.
Such research "may yield an understanding of what components of sporadic disease are defined by genetic characteristics," said Goldstein, professor in the Department of Cellular & Molecular Medicine, an HHMI investigator and director of UC San Diego's Stem Cell Program.
AD is now the seventh leading cause of death in the U.S., according to the National Centers for Health Statistics. The National Niemann-Pick Disease Foundation reports that children born with NPC rarely survive beyond the age of 20.
Lawrence S.B. Goldstein, Ph.D. presented "Human pluripotent stem cell models of Alzheimer's Disease and Niemann-Pick Type C," Minisymposium 28: ES Cells, iPS Cells, and Germ Cells, Abstract #2381.
Source: Cathy Yarbrough
American Society for Cell Biology
Predicting The Severity Of Disability From Stroke
A small difference in DNA sequence predicts the degree of disability after a stroke, according to a paper published online on February 28 in the Journal of Experimental Medicine. Stroke, the consequence of disturbed blood flow to the brain, can impair speech, movement and vision, but it is currently difficult for clinicians to predict the severity of these side effects or the long-term prognosis.
Strokes result in the death of brain cells called neurons. Angeles Almeida and co-workers found that variations in a gene known to control cell death - Tp53 - influence stroke outcome.
Tp53 comes in two flavors in humans: R and P. The R variant triggers cell death more efficiently. In two distinct groups of stroke patients, those exclusively expressing the R variant suffered more severe disability several months after the stroke. Neurons expressing the R variant were more vulnerable to death caused by oxygen deprivation, a condition that mimics the brain environment during stroke.
Future work is needed to determine if this Tp53 variation can also predict prognosis of patients with other disorders characterized by neuronal death, such as Alzheimer's or Parkinson's disease.
Notes:
Gomez-Sanchez, J.C., et al. 2011. J. Exp. Med. doi:10.1084/jem.20101523
Source:
Rita Sullivan
Rockefeller University Press
Strokes result in the death of brain cells called neurons. Angeles Almeida and co-workers found that variations in a gene known to control cell death - Tp53 - influence stroke outcome.
Tp53 comes in two flavors in humans: R and P. The R variant triggers cell death more efficiently. In two distinct groups of stroke patients, those exclusively expressing the R variant suffered more severe disability several months after the stroke. Neurons expressing the R variant were more vulnerable to death caused by oxygen deprivation, a condition that mimics the brain environment during stroke.
Future work is needed to determine if this Tp53 variation can also predict prognosis of patients with other disorders characterized by neuronal death, such as Alzheimer's or Parkinson's disease.
Notes:
Gomez-Sanchez, J.C., et al. 2011. J. Exp. Med. doi:10.1084/jem.20101523
Source:
Rita Sullivan
Rockefeller University Press
Chinese Herb Helps Dementia Patients
A herb used in China for centuries may help stroke patients suffering from dementia.
Experts tested the herbal medicine in a clinical trial and found it lived up to its reputation.
The drug, extracted from an orchid and six other plants, has been used since 100 AD for treating dizziness, headache and stroke. It was found to significantly increase mental function in a three-month study of 120 stroke patients.
The remedy, known as gastrodine compound granule, is the first herbal drug for dementia to be tested in clinical trials at hospitals in China. Doctors hope to find a cheaper alternative to Western medication that is more acceptable to Chinese people.
Jinzhou Tian of the Institute of Geriatrics, Beijing University of Chinese Medicine, said: 'Chemical drugs, such as cholinesterase inhibitors, are effective in the treatment of cognitive and memory function in dementia, but these drugs are expensive and have side effects.
'This study might result in doctors considering the use of herbal medications, such as gastrodine compound granules to supplement the treatment of mild and moderate cognitive impairment in primary care for the elderly with cerebral ischemic damage.'
Memory powers
Between 1 and 3 % of people in the world suffer from vascular dementia. It is a type of dementia caused by blood vessel disease or small strokes in the brain and results in problems with memory, thinking and behaviour and interferes with a person's ability to work and to carry out everyday tasks such as bathing, cooking and dressing.
All of the patients in the trial at Beijing Dongzhimen Hospital were suffering from mild to moderate vascular dementia after their stroke. Seventy patients received the herbal medicine while the others were given a drug known as Duxila which is normally used to treat stroke in China.
At the end of the study, the gastrodine group performed about the same as the Duxila group in tests of their mental state and behaviour. There were fewer side effects in the group taking the Chinese medicine, the doctors reported at a meeting of the American Heart Association's Second Asia Pacific Forum.
Experts tested the herbal medicine in a clinical trial and found it lived up to its reputation.
The drug, extracted from an orchid and six other plants, has been used since 100 AD for treating dizziness, headache and stroke. It was found to significantly increase mental function in a three-month study of 120 stroke patients.
The remedy, known as gastrodine compound granule, is the first herbal drug for dementia to be tested in clinical trials at hospitals in China. Doctors hope to find a cheaper alternative to Western medication that is more acceptable to Chinese people.
Jinzhou Tian of the Institute of Geriatrics, Beijing University of Chinese Medicine, said: 'Chemical drugs, such as cholinesterase inhibitors, are effective in the treatment of cognitive and memory function in dementia, but these drugs are expensive and have side effects.
'This study might result in doctors considering the use of herbal medications, such as gastrodine compound granules to supplement the treatment of mild and moderate cognitive impairment in primary care for the elderly with cerebral ischemic damage.'
Memory powers
Between 1 and 3 % of people in the world suffer from vascular dementia. It is a type of dementia caused by blood vessel disease or small strokes in the brain and results in problems with memory, thinking and behaviour and interferes with a person's ability to work and to carry out everyday tasks such as bathing, cooking and dressing.
All of the patients in the trial at Beijing Dongzhimen Hospital were suffering from mild to moderate vascular dementia after their stroke. Seventy patients received the herbal medicine while the others were given a drug known as Duxila which is normally used to treat stroke in China.
At the end of the study, the gastrodine group performed about the same as the Duxila group in tests of their mental state and behaviour. There were fewer side effects in the group taking the Chinese medicine, the doctors reported at a meeting of the American Heart Association's Second Asia Pacific Forum.
Gene testing doesn't increase anxiety, depression in children of people with Alzheimer's
Adult children of people with Alzheimer's disease were satisfied and unharmed by the experience of genetic risk
assessment, even when results suggested they might be at risk, according to new findings presented by Robert C. Green at the
recent International Conference on the Prevention of Dementia, sponsored by the Alzheimer's Association. Green, a medical
doctor and professor of neurology at Boston University School of Medicine, led the team that conducted the study.
The study focused on the psychological and behavioral impact of testing for the well-known risk marker for Alzheimer's
disease, ApoE4, one form of the apolipoprotein E (APOE) gene. When the team compared data from participants who had been told
they were either positive or negative for ApoE4 with those from participants who had not had their ApoE4 status disclosed to
them, the researchers found no significant difference in tests for depression and anxiety.
Moreover, 95 percent of participants reported that they would choose risk assessment again and 82 percent would recommend
risk assessment to family or friends.
"As new treatments are developed to delay the onset of Alzheimer's, it is going to be critical to identify those at greatest
risk," says Green. "At the same time, it will be very important that genetic risk assessment is done carefully and
communicated accurately so individuals feel empowered by the results and are able to maintain a positive outlook and a good
quality of life."
For the study, the researchers randomized 162 study participants from Boston into two groups -- one received assessment based
on age, family history, gender, and disclosed APOE genotype; and one received assessment based only on age, family history
and gender.
After one year, the team found no significant differences among the groups (ApoE4 positive, ApoE4 negative, or no disclosure)
when assessing them using the Center for Epidemiological Studies' Depression Scale and Beck Anxiety Inventory.
Those in the study who tested positive for ApoE4 and were alerted to their genetic status were 5.8 times more likely to have
altered their long-term care insurance than individuals who did not receive genotype disclosure.
"The study suggests that people who are armed with useful information about their possible future healthcare needs will take
steps to protect themselves financially," says Green.
According to Green and his team of researchers, the REVEAL study (Risk Evaluation and Education for Alzheimer's disease) is
the first randomized trial to examine the impact of providing risk assessment -- including APOE gene marker disclosure -- for
Alzheimer's disease. Their study was supported by the National Human Genome Research Institute and the National Institute on
Aging of the National Institutes of Health.
The Alzheimer's Association, the world leader in Alzheimer research and support, is the first and largest voluntary health
organization dedicated to finding prevention methods, treatments, and an eventual cure for Alzheimer's. For 25 years, the
association has provided information and care consultation, created supportive services for families, increased funding for
dementia research, and influenced public policy changes.
Boston University School of Medicine, founded in 1848, is a leading academic and research institution, with an enrollment of
nearly 1,000 students and more than 1,000 full-time faculty. Nationally renowned for its programs in heart disease,
hypertension, stroke, pulmonary disease, arthritis, Alzheimer's disease, autism, alcoholism and drug addiction, among others,
in the past year it ranked 13th among U.S. medical schools in total dollars of National Institutes of Health funding.
Contact: Gina DiGravio
Gina.Digraviobmc
617-638-8491
Boston University
bu
assessment, even when results suggested they might be at risk, according to new findings presented by Robert C. Green at the
recent International Conference on the Prevention of Dementia, sponsored by the Alzheimer's Association. Green, a medical
doctor and professor of neurology at Boston University School of Medicine, led the team that conducted the study.
The study focused on the psychological and behavioral impact of testing for the well-known risk marker for Alzheimer's
disease, ApoE4, one form of the apolipoprotein E (APOE) gene. When the team compared data from participants who had been told
they were either positive or negative for ApoE4 with those from participants who had not had their ApoE4 status disclosed to
them, the researchers found no significant difference in tests for depression and anxiety.
Moreover, 95 percent of participants reported that they would choose risk assessment again and 82 percent would recommend
risk assessment to family or friends.
"As new treatments are developed to delay the onset of Alzheimer's, it is going to be critical to identify those at greatest
risk," says Green. "At the same time, it will be very important that genetic risk assessment is done carefully and
communicated accurately so individuals feel empowered by the results and are able to maintain a positive outlook and a good
quality of life."
For the study, the researchers randomized 162 study participants from Boston into two groups -- one received assessment based
on age, family history, gender, and disclosed APOE genotype; and one received assessment based only on age, family history
and gender.
After one year, the team found no significant differences among the groups (ApoE4 positive, ApoE4 negative, or no disclosure)
when assessing them using the Center for Epidemiological Studies' Depression Scale and Beck Anxiety Inventory.
Those in the study who tested positive for ApoE4 and were alerted to their genetic status were 5.8 times more likely to have
altered their long-term care insurance than individuals who did not receive genotype disclosure.
"The study suggests that people who are armed with useful information about their possible future healthcare needs will take
steps to protect themselves financially," says Green.
According to Green and his team of researchers, the REVEAL study (Risk Evaluation and Education for Alzheimer's disease) is
the first randomized trial to examine the impact of providing risk assessment -- including APOE gene marker disclosure -- for
Alzheimer's disease. Their study was supported by the National Human Genome Research Institute and the National Institute on
Aging of the National Institutes of Health.
The Alzheimer's Association, the world leader in Alzheimer research and support, is the first and largest voluntary health
organization dedicated to finding prevention methods, treatments, and an eventual cure for Alzheimer's. For 25 years, the
association has provided information and care consultation, created supportive services for families, increased funding for
dementia research, and influenced public policy changes.
Boston University School of Medicine, founded in 1848, is a leading academic and research institution, with an enrollment of
nearly 1,000 students and more than 1,000 full-time faculty. Nationally renowned for its programs in heart disease,
hypertension, stroke, pulmonary disease, arthritis, Alzheimer's disease, autism, alcoholism and drug addiction, among others,
in the past year it ranked 13th among U.S. medical schools in total dollars of National Institutes of Health funding.
Contact: Gina DiGravio
Gina.Digraviobmc
617-638-8491
Boston University
bu
Scientists Discover Possible Link Between Oxidative Stress And Non-hereditary Degenerative Disease
The irreversible neurological degeneration associated with Parkinson's and Alzheimer's diseases may be the consequence of oxidative stress--the imbalance of antioxidants and pro-oxidants in cells. This imbalance results in an excess of reactive oxygen species--harmful oxygen-containing molecules that can cause damage to proteins. In the April issue of the Journal of Biological Chemistry, scientists from the Emory University School of Medicine report that the protein DJ-1 is oxidatively damaged in non-hereditary (sporadic) Parkinson's disease.
While scientists do not know the function of DJ-1, they have previously identified abnormalities in DJ-1 that directly cause hereditary (familial) Parkinson's disease. About 10 percent of Parkinson's disease cases are hereditary forms caused by either a genetic deletion or mutations that result in amino acid substitutions, which can dramatically affect protein structure or function.
The cause of the 90 percent of Parkinson's Disease cases not influenced by genetics has remained more of a mystery. Lian Li, PhD, is associate professor of pharmacology at Emory University School of Medicine and lead author of this study, which was funded by a grant from the National Institutes of Health. "One popular theory has suggested that these sporadic cases result from exposure to environmental toxins, such as herbicides or pesticides," she says. "Previous research has indicated that these toxins lead to oxidative stress. While oxidative stress does occur naturally as humans age, further oxidation caused by toxins may overwhelm the body?•s antioxidants."
Until now, attempts to link environmental toxins to oxidation and neurological disorders have been only somewhat successful, in part because scientists have been unable to identify the molecular target of oxidation. "This theory [that toxins cause oxidative stress] has been around for a long time," says Dr. Li. "But what?•s been damaged by this oxidative stress?"
Aware of the connection between DJ-1 mutations and familial Parkinson's disease, Dr. Li and her collaborators examined the oxidation levels of the protein in sporadic cases. Their hypothesis that DJ-1 was the missing link proved to be correct: DJ-1 in patients who had Parkinson's disease showed signs of oxidative damage, including structural changes as the protein accumulated additional oxygen molecules (carbonylation and methonine oxidation).
These modifications to DJ-1 caused by the oxidative stress are irreversible and irreparable. Like familial Parkinson's disease, the structural changes to the DJ-1 protein in sporadic Parkinson's disease signal an abnormality, leading to the eventual degradation and loss of the protein. "The protein unfolds and cannot function normally," Dr. Li explains. "Not recognizing the unfamiliar shape, the protein is broken down by the cell. The end result is the same: you lose your protein. Any mutation or modification causing this protein to lose its function will then lead to neurodegeneration in Parkinson's disease."
Now that Dr. Li and her team are clear that a relationship between DJ-1 and neurodegeneration exists, they are preparing to extend their examination into the protein's role. Based on biochemical analysis, Dr. Li believes DJ-1 may serve as a protease, activating and deactivating a protein by cleaving the bonds that connect its amino acids. Dr. Li is also currently exploring the possibility that DJ-1 may serve as an antioxidant, and that when mutated or damaged, the protein cannot defend the cell.
Future information about the role of DJ-1 may enable the development of drugs to specifically target the protein, perhaps stopping or reversing Parkinson's disease or Alzheimer's disease, which also may be impacted by the oxidation of DJ-1. In the meantime, says Dr. Li, people looking to prevent neurological degeneration might do well by looking to the kitchen cabinet, not the pharmacy: green tea and vitamin C supplements are two bountiful sources of antioxidants.
Contact: Holly Korschun
Emory University Health Sciences Center
While scientists do not know the function of DJ-1, they have previously identified abnormalities in DJ-1 that directly cause hereditary (familial) Parkinson's disease. About 10 percent of Parkinson's disease cases are hereditary forms caused by either a genetic deletion or mutations that result in amino acid substitutions, which can dramatically affect protein structure or function.
The cause of the 90 percent of Parkinson's Disease cases not influenced by genetics has remained more of a mystery. Lian Li, PhD, is associate professor of pharmacology at Emory University School of Medicine and lead author of this study, which was funded by a grant from the National Institutes of Health. "One popular theory has suggested that these sporadic cases result from exposure to environmental toxins, such as herbicides or pesticides," she says. "Previous research has indicated that these toxins lead to oxidative stress. While oxidative stress does occur naturally as humans age, further oxidation caused by toxins may overwhelm the body?•s antioxidants."
Until now, attempts to link environmental toxins to oxidation and neurological disorders have been only somewhat successful, in part because scientists have been unable to identify the molecular target of oxidation. "This theory [that toxins cause oxidative stress] has been around for a long time," says Dr. Li. "But what?•s been damaged by this oxidative stress?"
Aware of the connection between DJ-1 mutations and familial Parkinson's disease, Dr. Li and her collaborators examined the oxidation levels of the protein in sporadic cases. Their hypothesis that DJ-1 was the missing link proved to be correct: DJ-1 in patients who had Parkinson's disease showed signs of oxidative damage, including structural changes as the protein accumulated additional oxygen molecules (carbonylation and methonine oxidation).
These modifications to DJ-1 caused by the oxidative stress are irreversible and irreparable. Like familial Parkinson's disease, the structural changes to the DJ-1 protein in sporadic Parkinson's disease signal an abnormality, leading to the eventual degradation and loss of the protein. "The protein unfolds and cannot function normally," Dr. Li explains. "Not recognizing the unfamiliar shape, the protein is broken down by the cell. The end result is the same: you lose your protein. Any mutation or modification causing this protein to lose its function will then lead to neurodegeneration in Parkinson's disease."
Now that Dr. Li and her team are clear that a relationship between DJ-1 and neurodegeneration exists, they are preparing to extend their examination into the protein's role. Based on biochemical analysis, Dr. Li believes DJ-1 may serve as a protease, activating and deactivating a protein by cleaving the bonds that connect its amino acids. Dr. Li is also currently exploring the possibility that DJ-1 may serve as an antioxidant, and that when mutated or damaged, the protein cannot defend the cell.
Future information about the role of DJ-1 may enable the development of drugs to specifically target the protein, perhaps stopping or reversing Parkinson's disease or Alzheimer's disease, which also may be impacted by the oxidation of DJ-1. In the meantime, says Dr. Li, people looking to prevent neurological degeneration might do well by looking to the kitchen cabinet, not the pharmacy: green tea and vitamin C supplements are two bountiful sources of antioxidants.
Contact: Holly Korschun
Emory University Health Sciences Center
Investment In GP Training And Memory Clinics For Those With Dementia - Response By Charity "For Dementia", UK
Barbara Stephens, Chief Executive of for dementia, the charity responsible for Admiral Nurses says:
"Dementia is a complex condition with many and varied causes. There needs to be a comprehensive and co-ordinated response to address this major public health issue."
"More training for GPs will, of course, help to identify more people in the early stages of the illness and will improve access to memory clinic and assessment services; however many people do not actively seek help when they are worried about their memory and it might be many months or even years before they receive any support.
Many families struggle with the condition for years, putting off the day they express their own or their loved ones concerns about this illness, which still carries such a stigma.
"Older family members, those most likely to develop a form of dementia, may already be coming into contact with health, care or housing services of some kind. It is therefore imperative that professionals 'in the round' are also trained to pick up these early signs and raise the issues."
"for dementia and Admiral Nurses look forward to the publication of the National Dementia Strategy expected early in the New Year and to working as part of the team with Government to ensure that the needs of this highly vulnerable and growing population group and their carers are fully addressed and that the funding is in place to bring it to reality. for dementia and Admiral Nurses are ready to play their part ."
"A key part of the Admiral Nurse's job is to act as a resource for all health and social care professionals in the locality. Formal and informal training and support is all in a day's work for an Admiral Nurse.
"In the meantime, anyone worried about their own or a loved one's memory and the prospect of dementia, and professional carers can call the Admiral Nursing DIRECT telephone and email helpline which is open 'extra hours' between Christmas and New Year."
Professional and family carers can call the dedicated Admiral Nursing DIRECT phone line 0845 257 9406 to talk to an experienced Admiral Nurse on Tuesday daytime 10 am- 4 pm, and Tuesday and Thursday evenings between 6pm and 9pm, or email questions to directfordementia.uk. For more information log on to fordementia.uk. The helpline and email service are open at extra times between Christmas and New Year.
Admiral Nurses and their role in conjunction with Memory Clinics.
Admiral Nurses offer a service that complements that provided by other members of the Memory Assessment Service (including Memory Clinics), by providing:
-- Specialist assessment of family carer's needs
-- Therapeutic support for those families presenting with complex problems and relationship issues
-- 'Step-up' facilitative support and liaison consultancy for people with dementia / family carers being referred on to secondary mental health services, where appropriate
-- 'Step-down' facilitative support and liaison consultancy with primary care services for people with dementia / family carers not eligible for medication at the time of assessment
Supporting the dementia journey
Admiral Nurses further complement the work of Memory Assessment Services by:
-- Monitoring of people with dementia at early to moderate stage; timely re-referral to Memory Assessment Service and/or referral to secondary mental health services, if appropriate.
-- Providing in-reach to primary care professionals, providing clinical advice, education and consultancy on dementia and carers' issues.
-- Offering health promotion and education for carers of people with dementia within primary care.
-- Facilitating information and support programmes for carers and people with dementia at primary care level
Admiral Nurses have a role throughout the dementia journey and can receive back referrals in the latter stages whilst also supporting families who never fulfil the criteria for secondary mental health carer services:
-- Providing support and consultancy for primary care professionals around advance care planning and end-of life decision-making.
-- Home support for family carers and people with dementia living in the community: facilitating end-of-life decision-making and clinical intervention; supporting the input of District Nurses and liaising with Palliative Care services where appropriate
-- Outreach support for residential and nursing care providers: supporting care-staff and families around end-of-life decision making and appropriate clinical interventions, liaising with primary care and Palliative Care services, as appropriate.
Admiral Nursing works in partnership with local service providers and work within the context of community based provision. The Admiral Nurses' Case Management Model underpins the work of Admiral Nurses, recognising the changing need over time of families affected by dementia. The model provides for increased input by Admiral Nurses at times of greater need, often associated with transitions in the journey such as at diagnosis, use of respite services, entry into care and bereavement.
About the charity for dementia
Admiral Nurses work within health and social care trust and are supported in their training and professional development by the charity for dementia. The mission of for dementia is to improve the quality of life of people with dementia by promoting and developing Admiral Nursing; providing high quality training and promoting best practice for professionals working with older people, carers and people with dementia; and supporting the Uniting Carers network through giving carers a voice
fordementia.uk
"Dementia is a complex condition with many and varied causes. There needs to be a comprehensive and co-ordinated response to address this major public health issue."
"More training for GPs will, of course, help to identify more people in the early stages of the illness and will improve access to memory clinic and assessment services; however many people do not actively seek help when they are worried about their memory and it might be many months or even years before they receive any support.
Many families struggle with the condition for years, putting off the day they express their own or their loved ones concerns about this illness, which still carries such a stigma.
"Older family members, those most likely to develop a form of dementia, may already be coming into contact with health, care or housing services of some kind. It is therefore imperative that professionals 'in the round' are also trained to pick up these early signs and raise the issues."
"for dementia and Admiral Nurses look forward to the publication of the National Dementia Strategy expected early in the New Year and to working as part of the team with Government to ensure that the needs of this highly vulnerable and growing population group and their carers are fully addressed and that the funding is in place to bring it to reality. for dementia and Admiral Nurses are ready to play their part ."
"A key part of the Admiral Nurse's job is to act as a resource for all health and social care professionals in the locality. Formal and informal training and support is all in a day's work for an Admiral Nurse.
"In the meantime, anyone worried about their own or a loved one's memory and the prospect of dementia, and professional carers can call the Admiral Nursing DIRECT telephone and email helpline which is open 'extra hours' between Christmas and New Year."
Professional and family carers can call the dedicated Admiral Nursing DIRECT phone line 0845 257 9406 to talk to an experienced Admiral Nurse on Tuesday daytime 10 am- 4 pm, and Tuesday and Thursday evenings between 6pm and 9pm, or email questions to directfordementia.uk. For more information log on to fordementia.uk. The helpline and email service are open at extra times between Christmas and New Year.
Admiral Nurses and their role in conjunction with Memory Clinics.
Admiral Nurses offer a service that complements that provided by other members of the Memory Assessment Service (including Memory Clinics), by providing:
-- Specialist assessment of family carer's needs
-- Therapeutic support for those families presenting with complex problems and relationship issues
-- 'Step-up' facilitative support and liaison consultancy for people with dementia / family carers being referred on to secondary mental health services, where appropriate
-- 'Step-down' facilitative support and liaison consultancy with primary care services for people with dementia / family carers not eligible for medication at the time of assessment
Supporting the dementia journey
Admiral Nurses further complement the work of Memory Assessment Services by:
-- Monitoring of people with dementia at early to moderate stage; timely re-referral to Memory Assessment Service and/or referral to secondary mental health services, if appropriate.
-- Providing in-reach to primary care professionals, providing clinical advice, education and consultancy on dementia and carers' issues.
-- Offering health promotion and education for carers of people with dementia within primary care.
-- Facilitating information and support programmes for carers and people with dementia at primary care level
Admiral Nurses have a role throughout the dementia journey and can receive back referrals in the latter stages whilst also supporting families who never fulfil the criteria for secondary mental health carer services:
-- Providing support and consultancy for primary care professionals around advance care planning and end-of life decision-making.
-- Home support for family carers and people with dementia living in the community: facilitating end-of-life decision-making and clinical intervention; supporting the input of District Nurses and liaising with Palliative Care services where appropriate
-- Outreach support for residential and nursing care providers: supporting care-staff and families around end-of-life decision making and appropriate clinical interventions, liaising with primary care and Palliative Care services, as appropriate.
Admiral Nursing works in partnership with local service providers and work within the context of community based provision. The Admiral Nurses' Case Management Model underpins the work of Admiral Nurses, recognising the changing need over time of families affected by dementia. The model provides for increased input by Admiral Nurses at times of greater need, often associated with transitions in the journey such as at diagnosis, use of respite services, entry into care and bereavement.
About the charity for dementia
Admiral Nurses work within health and social care trust and are supported in their training and professional development by the charity for dementia. The mission of for dementia is to improve the quality of life of people with dementia by promoting and developing Admiral Nursing; providing high quality training and promoting best practice for professionals working with older people, carers and people with dementia; and supporting the Uniting Carers network through giving carers a voice
fordementia.uk
Alzheimer Scotland Responds To NICE Court Date On Dementia Drugs
Alzheimer Scotland welcomes news that a fast-track hearing has been ordered for a High Court challenge to the refusal of the National Institute for Clinical Excellence (NICE) to back dementia drugs for thousands of people on the NHS. NICE has argued that such recommendations were made because the drugs concerned "were not particularly effective for people with mild Alzheimer's disease," and that resources would be more effectively used for other treatments. Although NICE is based in England, its recommendations are adopted by NHS Quality Improvement Scotland for implementation north of the border. The four day hearing will commence on 25th June 2007.
Despite NICE's request for a later court date, on the basis of difficulties securing barristers for the judicial review, Deputy High Court judge James Goudie QC ruled that the landmark case must take place in June, due to its public importance and "exceptional urgency."
Earlier this year the High Court granted permission to proceed to a Judicial Review on the following three grounds:
-- Procedural: since NICE has repeatedly refused to disclose a fully working version of the cost effectiveness model used to determine the value of treatment in patients with mild Alzheimer's disease, the process leading to the Final Appraisal Determination (FAD) and the new treatment guidance breached the principles of procedural fairness
-- Irrationality: some of the assumptions made or conclusions drawn in the FAD are irrational or cannot be supported
-- Human Rights/Discrimination: the use of MMSE (Mini Mental State Examination) scores as a rigid tool to determine access to treatment discriminates against certain patient groups
Jim Jackson, Chief Executive of Alzheimer Scotland, greeted this news with cautious optimism,
"We welcome the promptness of the judicial review and the recognition of its importance by Judge Goudie. These drugs have a positive part to play in moderating the effects of early-to-moderate stage Alzheimer's disease for many people. They have already led to earlier diagnoses for people with dementia across Scotland. The removal of these early treatments will be step backwards for dementia care in Scotland."
From the Alzheimer Scotland Dementia Manifesto 2007:
Let's make dementia a priority
Scottish clinical guidelines* recommend drugs for people in the early stages of Alzheimer's disease; but the NHS won't pay. The cost? About ??1,000 a year per person to the NHS. The benefit? For those the drugs help, the chance to function as normally as possible for as long as they can, to stay independent and to make legal and financial arrangements, saving expense and heartache for them and their families now and in the future. Early treatment is the only chance people have of getting back close to their normal ability - there is no chance of this if they have to wait.
If dementia affected people in their 20s, would they have to wait until they were seriously impaired before getting treatment?
Carers facing the challenges of looking after someone with severe dementia are also denied the chance to see if Alzheimer's disease drugs might help. They need all the help they can get.
Denying people the drugs they need on the NHS will increase health inequality, as only those who can afford to pay get the treatment they need.
About dementia:
-- Dementia affects approximately 58,000 people in Scotland.
-- Alzheimer's disease is the main form of dementia.
-- The second most common is vascular dementia.
-- As yet there is no cure.
About Alzheimer Scotland
Alzheimer Scotland is Scotland's foremost voluntary organisation working for people with dementia and their carers. It:
-- speaks out for the rights and concerns of people with dementia and their carers;
-- operates services on over 60 sites throughout Scotland providing practical services such as day, evening and weekend centres, home care and befriending and carers' support services;
-- provides the 24 hour national freephone Dementia Helpline (0808 808 3000);
-- provides the website alzscot;
-- supports a network of over 40 carers' support groups;
-- provides information to carers, professionals and people with dementia;
-- publishes leaflets, booklets, reports and a quarterly newsletter keeping carers and professionals up-to-date
-- has a research programme.
Freephone 24hr Dementia Helpline telephone number: (UK) 0808 808 3000
alzscot
Despite NICE's request for a later court date, on the basis of difficulties securing barristers for the judicial review, Deputy High Court judge James Goudie QC ruled that the landmark case must take place in June, due to its public importance and "exceptional urgency."
Earlier this year the High Court granted permission to proceed to a Judicial Review on the following three grounds:
-- Procedural: since NICE has repeatedly refused to disclose a fully working version of the cost effectiveness model used to determine the value of treatment in patients with mild Alzheimer's disease, the process leading to the Final Appraisal Determination (FAD) and the new treatment guidance breached the principles of procedural fairness
-- Irrationality: some of the assumptions made or conclusions drawn in the FAD are irrational or cannot be supported
-- Human Rights/Discrimination: the use of MMSE (Mini Mental State Examination) scores as a rigid tool to determine access to treatment discriminates against certain patient groups
Jim Jackson, Chief Executive of Alzheimer Scotland, greeted this news with cautious optimism,
"We welcome the promptness of the judicial review and the recognition of its importance by Judge Goudie. These drugs have a positive part to play in moderating the effects of early-to-moderate stage Alzheimer's disease for many people. They have already led to earlier diagnoses for people with dementia across Scotland. The removal of these early treatments will be step backwards for dementia care in Scotland."
From the Alzheimer Scotland Dementia Manifesto 2007:
Let's make dementia a priority
Scottish clinical guidelines* recommend drugs for people in the early stages of Alzheimer's disease; but the NHS won't pay. The cost? About ??1,000 a year per person to the NHS. The benefit? For those the drugs help, the chance to function as normally as possible for as long as they can, to stay independent and to make legal and financial arrangements, saving expense and heartache for them and their families now and in the future. Early treatment is the only chance people have of getting back close to their normal ability - there is no chance of this if they have to wait.
If dementia affected people in their 20s, would they have to wait until they were seriously impaired before getting treatment?
Carers facing the challenges of looking after someone with severe dementia are also denied the chance to see if Alzheimer's disease drugs might help. They need all the help they can get.
Denying people the drugs they need on the NHS will increase health inequality, as only those who can afford to pay get the treatment they need.
About dementia:
-- Dementia affects approximately 58,000 people in Scotland.
-- Alzheimer's disease is the main form of dementia.
-- The second most common is vascular dementia.
-- As yet there is no cure.
About Alzheimer Scotland
Alzheimer Scotland is Scotland's foremost voluntary organisation working for people with dementia and their carers. It:
-- speaks out for the rights and concerns of people with dementia and their carers;
-- operates services on over 60 sites throughout Scotland providing practical services such as day, evening and weekend centres, home care and befriending and carers' support services;
-- provides the 24 hour national freephone Dementia Helpline (0808 808 3000);
-- provides the website alzscot;
-- supports a network of over 40 carers' support groups;
-- provides information to carers, professionals and people with dementia;
-- publishes leaflets, booklets, reports and a quarterly newsletter keeping carers and professionals up-to-date
-- has a research programme.
Freephone 24hr Dementia Helpline telephone number: (UK) 0808 808 3000
alzscot
The Blanchette Rockefeller Neurosciences Institute Identifies Groundbreaking New Therapies For Prevention And Treatment Of Alzheimer's Disease
A Blanchette Rockefeller Neurosciences Institute (BRNI) study published in the Journal of Neuroscience reveals underlying causes for the degeneration of synapses in Alzheimer's Disease and identifies promising pharmaceutical solutions for the devastating condition that affects more than 5 million people in the United States. The BRNI study is the first to achieve fundamental molecular understanding of how synapses are lost in Alzheimer's Disease before the plaques and tangles develop. At the same time, it is the first study to demonstrate the comprehensive benefits of synaptogenic compounds in treating Alzheimer's Disease.
The BRNI study marks an important shift in our understanding of how Alzheimer's Disease is caused and should be treated. Previous autopsy-based studies have shown the critical role of synaptic loss in producing dementia (though, not the reason behind the degeneration), yet for decades scientists and pharmaceutical companies have focused on ways to target the amyloid plaques and neurofibrillary tangles thought to play a role in causing Alzheimer's Disease. By preventing the loss of synapses, BRNI's new therapeutics prevent the progressive symptoms of Alzheimer's Disease.
"Alzheimer's Disease is not primarily a disease of plaques and tangles as many had previously concluded, it is most importantly a disease of synapses," said Dr. Daniel Alkon, the scientific director of BRNI and co-author of the study, "This study found that treatments that target the loss of synapses in the Alzheimer's brain, can virtually eliminate all other elements of the disease elevation of the toxic protein, A Beta, the loss of neurons, the appearance of plaques, and loss of cognitive function; the animals' brains were normalized."
The study utilized mice genetically engineered to express the symptoms and pathology of human Alzheimer's Disease in two different strains. BRNI used a difficult training regimen for the mice in order to reveal that significant cognitive deficits occurred five months before plaques were detected in their brains, providing evidence that plaques and tangles are not at the root of the disease.
Treatments of Bryostatin and similar compounds synthesized at BRNI that target the enzyme PKCepsilon, which controls the creation of synapses at the molecular level, were administered for twelve weeks during the study. While the compounds promoted the growth of new synapses and preservation of existing synapses, they also stopped the decrease of PKCepsilon and the increase of soluble beta amyloid, meaning that the treatments could be used to prevent the familiar hallmarks of Alzheimer's Disease, the plaques and tangles. BRNI has received approval to move forward with Phase II clinical testing for Bryostatin to treat Alzheimer's Disease, which is set to begin within the next several months.
Source: Blanchette Rockefeller Neurosciences Institute
The BRNI study marks an important shift in our understanding of how Alzheimer's Disease is caused and should be treated. Previous autopsy-based studies have shown the critical role of synaptic loss in producing dementia (though, not the reason behind the degeneration), yet for decades scientists and pharmaceutical companies have focused on ways to target the amyloid plaques and neurofibrillary tangles thought to play a role in causing Alzheimer's Disease. By preventing the loss of synapses, BRNI's new therapeutics prevent the progressive symptoms of Alzheimer's Disease.
"Alzheimer's Disease is not primarily a disease of plaques and tangles as many had previously concluded, it is most importantly a disease of synapses," said Dr. Daniel Alkon, the scientific director of BRNI and co-author of the study, "This study found that treatments that target the loss of synapses in the Alzheimer's brain, can virtually eliminate all other elements of the disease elevation of the toxic protein, A Beta, the loss of neurons, the appearance of plaques, and loss of cognitive function; the animals' brains were normalized."
The study utilized mice genetically engineered to express the symptoms and pathology of human Alzheimer's Disease in two different strains. BRNI used a difficult training regimen for the mice in order to reveal that significant cognitive deficits occurred five months before plaques were detected in their brains, providing evidence that plaques and tangles are not at the root of the disease.
Treatments of Bryostatin and similar compounds synthesized at BRNI that target the enzyme PKCepsilon, which controls the creation of synapses at the molecular level, were administered for twelve weeks during the study. While the compounds promoted the growth of new synapses and preservation of existing synapses, they also stopped the decrease of PKCepsilon and the increase of soluble beta amyloid, meaning that the treatments could be used to prevent the familiar hallmarks of Alzheimer's Disease, the plaques and tangles. BRNI has received approval to move forward with Phase II clinical testing for Bryostatin to treat Alzheimer's Disease, which is set to begin within the next several months.
Source: Blanchette Rockefeller Neurosciences Institute
Revealing Lithium's Mode Of Action
Though it has been prescribed for over 50 years to treat bipolar disorder, there are still many questions regarding exactly how lithium works. However, in a study appearing in this month's Journal of Lipid Research, researchers have provided solid evidence that lithium reduces brain inflammation by adjusting the metabolism of the health-protective omega-3-fatty acid called DHA.
Inflammation in the brain, like other parts of the body, is an important process to help the brain combat infection or injury. However, excess or unwanted inflammation can damage sensitive brain cells, which can contribute to psychiatric conditions like bipolar disorder or degenerative diseases like Alzheimers.
It's believed that lithium helps treat bipolar disorder by reducing brain inflammation during the manic phase, thus alleviating some of the symptoms. Exactly how lithium operates, though, has been debated.
Mireille Basselin and colleagues at the National Institute of Aging and University of Colorado, Denver, took a detailed approach to this question by using mass spectrometry analysis to analyze the chemical composition of brain samples of both control and lithium-treated rats stressed by brain inflammation.
They found that in agreement with some other studies, rats given a six-week lithium treatment had reduced levels of arachidonic acid and its products, which can contribute to inflammation.
In addition, they also demonstrated, for the first time, that lithium treatment increased levels of a metabolite called 17-OH-DHA in response to inflammation. 17-OH-DHA is formed from the omega-3 fatty acid DHA (docosahexaenoic acid) and is the precursor to a wide range of anti-inflammatory compounds known as docosanoids. Other anti-inflammatory drugs, like aspirin, are known to also enhance docosanoids in their mode of action.
Basselin and colleagues noted that the concentration of DHA did not increase, which suggests that lithium may increase 17-OH-DHA levels by affecting the enzyme that converts DHA to 17-OH-DHA.
By reducing both pro-inflammatory AA products, and increasing anti-inflammatory DHA products, lithium exerts a double-protective effect which may explain why it works well in bipolar treatment. Now that its mechanism is a little better understood, it may lead to additional uses for this chemical.
From the article: "Lithium modifies brain arachidonic and docosahexaenoic metabolism in rat lipopolysaccharide model of neuroinflammation" by Mireille Basselin, Hyung-Wook Kim, Mei Chen, Kaizong Ma, Stanley I. Rapoport, Robert C. Murphy and Santiago E. Farias
Source:
Nick Zagorski
American Society for Biochemistry and Molecular Biology
Inflammation in the brain, like other parts of the body, is an important process to help the brain combat infection or injury. However, excess or unwanted inflammation can damage sensitive brain cells, which can contribute to psychiatric conditions like bipolar disorder or degenerative diseases like Alzheimers.
It's believed that lithium helps treat bipolar disorder by reducing brain inflammation during the manic phase, thus alleviating some of the symptoms. Exactly how lithium operates, though, has been debated.
Mireille Basselin and colleagues at the National Institute of Aging and University of Colorado, Denver, took a detailed approach to this question by using mass spectrometry analysis to analyze the chemical composition of brain samples of both control and lithium-treated rats stressed by brain inflammation.
They found that in agreement with some other studies, rats given a six-week lithium treatment had reduced levels of arachidonic acid and its products, which can contribute to inflammation.
In addition, they also demonstrated, for the first time, that lithium treatment increased levels of a metabolite called 17-OH-DHA in response to inflammation. 17-OH-DHA is formed from the omega-3 fatty acid DHA (docosahexaenoic acid) and is the precursor to a wide range of anti-inflammatory compounds known as docosanoids. Other anti-inflammatory drugs, like aspirin, are known to also enhance docosanoids in their mode of action.
Basselin and colleagues noted that the concentration of DHA did not increase, which suggests that lithium may increase 17-OH-DHA levels by affecting the enzyme that converts DHA to 17-OH-DHA.
By reducing both pro-inflammatory AA products, and increasing anti-inflammatory DHA products, lithium exerts a double-protective effect which may explain why it works well in bipolar treatment. Now that its mechanism is a little better understood, it may lead to additional uses for this chemical.
From the article: "Lithium modifies brain arachidonic and docosahexaenoic metabolism in rat lipopolysaccharide model of neuroinflammation" by Mireille Basselin, Hyung-Wook Kim, Mei Chen, Kaizong Ma, Stanley I. Rapoport, Robert C. Murphy and Santiago E. Farias
Source:
Nick Zagorski
American Society for Biochemistry and Molecular Biology
How toxic proteins kill nerve cells in Alzheimer's patients' brains
Scientists have discovered how toxic proteins kill nerve cells in Alzheimer's patients' brains. The scientists hope their discovery will lead to new and more effective treatments for Alzheimer's patients.
You can read about this new research in the journal Science.
The accumulation of amyloid protein plagues is linked to Alzheimer's. According to findings in this new study, these plaques cause damage by interacting with an enzyme produced in the cell's energy-producing power plants.
This interaction damages the mitochondria, causing toxins to leak out, this causes the eventual destruction of the cell.
The scientists say that as the cells are lost so is memory and other symptoms associated with Alzheimer's.
The scientists analysed brain tissue from Alzheimer's patients as well as genetically engineered mice. The scientists say we should be able to, after some time, block or undermine the interaction between the amyloid plagues and the mitochondrial anzyme.
Significant step
Dr Susanne Sorensen, Alzheimer's Society Research Head said "The link between the occurrence of amyloid plaques in the brain and the death of nerve cells has seemed obvious for many years, but there has been no clear experimental evidence for a mechanism that would explain how amyloid beta cause the death of nerve cells. This paper provides a possible explanation of how amyloid beta may cause cell death and points towards potential targets for drug therapy. This is very basic, but very important research. There is currently no real treatment for Alzheimer's disease that halts or reverses the disease."
The research team in this study came from various parts of the world.
You can read about this new research in the journal Science.
The accumulation of amyloid protein plagues is linked to Alzheimer's. According to findings in this new study, these plaques cause damage by interacting with an enzyme produced in the cell's energy-producing power plants.
This interaction damages the mitochondria, causing toxins to leak out, this causes the eventual destruction of the cell.
The scientists say that as the cells are lost so is memory and other symptoms associated with Alzheimer's.
The scientists analysed brain tissue from Alzheimer's patients as well as genetically engineered mice. The scientists say we should be able to, after some time, block or undermine the interaction between the amyloid plagues and the mitochondrial anzyme.
Significant step
Dr Susanne Sorensen, Alzheimer's Society Research Head said "The link between the occurrence of amyloid plaques in the brain and the death of nerve cells has seemed obvious for many years, but there has been no clear experimental evidence for a mechanism that would explain how amyloid beta cause the death of nerve cells. This paper provides a possible explanation of how amyloid beta may cause cell death and points towards potential targets for drug therapy. This is very basic, but very important research. There is currently no real treatment for Alzheimer's disease that halts or reverses the disease."
The research team in this study came from various parts of the world.
Alzheimer's Society Fight To Avoid Leaving Vulnerable People In Lincs Without Vital Support
Alzheimer's Society is calling on Lincolnshire residents to help prevent those affected by dementia from being abandoned without support.
Alzheimer's Society is calling on Lincolnshire residents to help prevent those affected by dementia from being abandoned without support. The Society is deeply concerned that, as Lincolnshire County Council has not renewed contracts, Alzheimer's Society has been forced to close the services it provided for carers of people with dementia in the county. The Society is now actively calling for volunteers to join its campaign, help deliver alternative services and fundraise, to make sure that people affected by dementia are not left to cope alone.
Pat Johnson, 67, from South Lincolnshire, says,
'I'm utterly devastated at the news that our local Alzheimer's Society service is closing. I know I speak on behalf of the whole group when I say that without our local support worker's constant help and support, we will be lost. My husband has had Alzheimer's for six years so I can tell you that coping with someone that has dementia on a daily basis is challenging enough. How can Lincolnshire Council leave us with no support or help?'
Ian Howarth, Alzheimer's Society Area Manager - East Midlands says,
'It's unacceptable that we are forced to close our services. This will have a devastating effect on the community, as it's vital those affected by dementia receive the support they so desperately rely on.'
We understand the difficulties the current economic and political environment place on the council's decision making, but we will be campaigning to ensure that the council reinstate and expand statutory services to meet the needs outlined in Lincolnshire Dementia Strategy. Commissioners of services need to understand that a likely outcome of not providing services to support people through dementia is that they will reach 'crisis point', where they are unable to cope with the pressures of daily care and require even more costly emergency intervention.
Approximately 10,000 people have dementia in Lincolnshire, and for the three years to June 2010 Lincolnshire County Council contracted Alzheimer's Society to provide services to support some of those caring for them. Alzheimer's Society had expected services would be continued and even expanded to reach across the entire county, in line with the recently launched Lincolnshire Dementia Strategy. It therefore bore the costs of providing existing services, when the contract ended in June, in the hope that the funding gap would be a temporary arrangement.
As no new contracts have since been offered by Lincolnshire County Council to Alzheimer's Society, or any other organisations, to provide any dementia related services, it has become necessary for Alzheimer's Society to close its carer support groups. However, the Society refuses to stop campaigning for the needs of people affected by dementia and is calling for help from the local community to add their voice, fundraise and volunteer.
Alzheimer's Society hopes to be in a position to develop a new range of services next year to meet the need identified in Lincolnshire Dementia Strategy. This will increase the choice available to people affected by dementia, in addition to those available when statutory services are resumed.
Alzheimer's Society has formed a Community Dementia Forum in Lincolnshire where organisations such as Lincolnshire Police, as well as interested members of the community, can come together and plan ideas to address some of the issues that people affected by dementia face in the county. The first meeting will focus on issues related to people being confused and walking the streets alone.
Source:
Alzheimer's Society
Alzheimer's Society is calling on Lincolnshire residents to help prevent those affected by dementia from being abandoned without support. The Society is deeply concerned that, as Lincolnshire County Council has not renewed contracts, Alzheimer's Society has been forced to close the services it provided for carers of people with dementia in the county. The Society is now actively calling for volunteers to join its campaign, help deliver alternative services and fundraise, to make sure that people affected by dementia are not left to cope alone.
Pat Johnson, 67, from South Lincolnshire, says,
'I'm utterly devastated at the news that our local Alzheimer's Society service is closing. I know I speak on behalf of the whole group when I say that without our local support worker's constant help and support, we will be lost. My husband has had Alzheimer's for six years so I can tell you that coping with someone that has dementia on a daily basis is challenging enough. How can Lincolnshire Council leave us with no support or help?'
Ian Howarth, Alzheimer's Society Area Manager - East Midlands says,
'It's unacceptable that we are forced to close our services. This will have a devastating effect on the community, as it's vital those affected by dementia receive the support they so desperately rely on.'
We understand the difficulties the current economic and political environment place on the council's decision making, but we will be campaigning to ensure that the council reinstate and expand statutory services to meet the needs outlined in Lincolnshire Dementia Strategy. Commissioners of services need to understand that a likely outcome of not providing services to support people through dementia is that they will reach 'crisis point', where they are unable to cope with the pressures of daily care and require even more costly emergency intervention.
Approximately 10,000 people have dementia in Lincolnshire, and for the three years to June 2010 Lincolnshire County Council contracted Alzheimer's Society to provide services to support some of those caring for them. Alzheimer's Society had expected services would be continued and even expanded to reach across the entire county, in line with the recently launched Lincolnshire Dementia Strategy. It therefore bore the costs of providing existing services, when the contract ended in June, in the hope that the funding gap would be a temporary arrangement.
As no new contracts have since been offered by Lincolnshire County Council to Alzheimer's Society, or any other organisations, to provide any dementia related services, it has become necessary for Alzheimer's Society to close its carer support groups. However, the Society refuses to stop campaigning for the needs of people affected by dementia and is calling for help from the local community to add their voice, fundraise and volunteer.
Alzheimer's Society hopes to be in a position to develop a new range of services next year to meet the need identified in Lincolnshire Dementia Strategy. This will increase the choice available to people affected by dementia, in addition to those available when statutory services are resumed.
Alzheimer's Society has formed a Community Dementia Forum in Lincolnshire where organisations such as Lincolnshire Police, as well as interested members of the community, can come together and plan ideas to address some of the issues that people affected by dementia face in the county. The first meeting will focus on issues related to people being confused and walking the streets alone.
Source:
Alzheimer's Society
Fisher Scientists Discover Protein That Fuels Alzheimer's Disease, Promising New Treatments Expected
Researchers at the Fisher Center for Alzheimer's Disease Research laboratory published "Gamma-secretase Activating Protein is a Therapeutic Target for Alzheimer's Disease" in Nature online. Drs. Gen He (lead author) and Paul Greengard have discovered a protein that stimulates the production of beta-amyloid, and therefore represents a major new advance in Alzheimer's disease research.
The protein, called gamma-secretase activating protein (gSAP), is expected to become a major target for anti-amyloid drugs that inhibit the brain's ability to produce toxic beta amyloid in Alzheimer's disease. Beta-amyloid is a substance found in the brain that becomes toxic in Alzheimer's disease and is responsible for most of the devastating symptoms of the disease. The researchers also discovered that gSAP is a target of the anti-cancer drug, Gleevec, which Fisher scientists previously showed could lower beta-amyloid levels in the brain. The new study showed that Gleevec lowers beta-amyloid production by binding to gSAP and preventing it from activating an enzyme called gamma-secretase, which is responsible for producing beta-amyloid. In addition, the researchers showed that the inhibition of gSAP is not toxic to nerve cells, unlike many other experimental beta-amyloid inhibitor drugs that produce severe toxic reactions. Hence, gSAP holds the promise of discovering highly specific anti-beta-amyloid drugs that will be safe to patients.
"Millions of people suffer from Alzheimer's disease, and treatment options are limited," says Dr. Paul Greengard, Nobel Laureate and Director of the Fisher Center for Alzheimer's Disease Research laboratory at The Rockefeller University. "Existing drugs may mask symptoms for a time but do nothing to stop the relentless downward progression of Alzheimer's. What is needed are safe and effective medications that will halt the cause of the underlying disease. It is our hope that this gamma-secretase activating protein will greatly add to the creation of safe and effective Alzheimer's treatments."
Kent Karosen, President of the Fisher Center for Alzheimer's Research Foundation says, "We are so proud of the scientists we support, and would like to specifically congratulate Drs. He and Greengard for discovering this important protein. Their latest research is a potential paradigm shift in how scientists and doctors around the world will attack Alzheimer's."
The Fisher Center for Alzheimer's Research Foundation is a leading source of funding for Alzheimer's research and education. We serve Alzheimer's patients and their families by seeking to understand the causes of, discover a cure for, and improve the lives of people with Alzheimer's disease. Nobel laureate Dr. Paul Greengard directs the Foundation's team of internationally renowned scientists, who have been at the forefront of research providing the conceptual framework for understanding Alzheimer's disease. The Fisher Center for Alzheimer's Research Foundation actively raises funds for Alzheimer's for these purposes. Of the money raised by the Foundation, only 8 cents out of every dollar is used for overhead and administrative purposes.
Source: Alzheimer's Research Foundation
View drug information on Gleevec.
The protein, called gamma-secretase activating protein (gSAP), is expected to become a major target for anti-amyloid drugs that inhibit the brain's ability to produce toxic beta amyloid in Alzheimer's disease. Beta-amyloid is a substance found in the brain that becomes toxic in Alzheimer's disease and is responsible for most of the devastating symptoms of the disease. The researchers also discovered that gSAP is a target of the anti-cancer drug, Gleevec, which Fisher scientists previously showed could lower beta-amyloid levels in the brain. The new study showed that Gleevec lowers beta-amyloid production by binding to gSAP and preventing it from activating an enzyme called gamma-secretase, which is responsible for producing beta-amyloid. In addition, the researchers showed that the inhibition of gSAP is not toxic to nerve cells, unlike many other experimental beta-amyloid inhibitor drugs that produce severe toxic reactions. Hence, gSAP holds the promise of discovering highly specific anti-beta-amyloid drugs that will be safe to patients.
"Millions of people suffer from Alzheimer's disease, and treatment options are limited," says Dr. Paul Greengard, Nobel Laureate and Director of the Fisher Center for Alzheimer's Disease Research laboratory at The Rockefeller University. "Existing drugs may mask symptoms for a time but do nothing to stop the relentless downward progression of Alzheimer's. What is needed are safe and effective medications that will halt the cause of the underlying disease. It is our hope that this gamma-secretase activating protein will greatly add to the creation of safe and effective Alzheimer's treatments."
Kent Karosen, President of the Fisher Center for Alzheimer's Research Foundation says, "We are so proud of the scientists we support, and would like to specifically congratulate Drs. He and Greengard for discovering this important protein. Their latest research is a potential paradigm shift in how scientists and doctors around the world will attack Alzheimer's."
The Fisher Center for Alzheimer's Research Foundation is a leading source of funding for Alzheimer's research and education. We serve Alzheimer's patients and their families by seeking to understand the causes of, discover a cure for, and improve the lives of people with Alzheimer's disease. Nobel laureate Dr. Paul Greengard directs the Foundation's team of internationally renowned scientists, who have been at the forefront of research providing the conceptual framework for understanding Alzheimer's disease. The Fisher Center for Alzheimer's Research Foundation actively raises funds for Alzheimer's for these purposes. Of the money raised by the Foundation, only 8 cents out of every dollar is used for overhead and administrative purposes.
Source: Alzheimer's Research Foundation
View drug information on Gleevec.
Journal Of Alzheimer's Disease Annual Award For Outstanding Contribution Awarded To John P. Cogswell, Ph.D.
John P. Cogswell, PhD, has been chosen as the recipient of the 2009 Alzheimer Award presented by the Journal of Alzheimer's Disease in recognition of his outstanding work, "Identification of miRNA changes in Alzheimer's disease brain and CSF yields putative biomarkers and insights into disease pathways" (J Alzheimers Dis 14: 27-41, 2008) by J.P. Cogswell et al.
"My co-authors and I are extremely pleased to have been chosen by a distinguished group of our peers as the recipients of this year's Journal of Alzheimer's Disease award for our work on the use of biomarkers in the diagnosis of AD," said Dr. Cogswell.
Each year the Associate Editors of the Journal of Alzheimer's Disease select an outstanding article from the previous year's volume to receive this prestigious award, which is made possible by support from IOS Press and Elan Pharmaceuticals. Dr. Cogswell will be presented with the bronze Alzheimer Medal with the likeness of Alois Alzheimer and a cash award.
Dr. Cogswell's work examines changes in microRNA expression and their role in the sporadic form of the disease. MicroRNAs are small regulatory RNAs that affect many basic cellular and biological processes. They are best known for regulating RNA and protein expression in pathways and networks due to the combinatorial binding potential between microRNAs and their targets. Using a sensitive and specific qRT-PCR technology this paper demonstrates altered expression of specific microRNAs in the brain of Alzheimer's disease (AD) subjects. The changes were both dependent and independent of the pathological changes with some detected quite early in the disease. Many of the microRNAs have functional roles in known AD pathways including neuronal differentiation, glutamate, and innate immunity although the potential combinatorial effects on insulin signaling were noteworthy.
Because of the need for diagnostic biomarkers of disease progression this paper additionally examines the microRNAs in the cerebrospinal fluid of late stage AD patients. Again AD-specific changes were detected although here microRNAs with known and potential combinatorial effects on T lymphocyte signaling and inflammation pathways were identified. Because the CSF contains memory T cells and antigen presenting cells involved in immune-surveillance of the brain, these data suggested that microRNA responses in CSF cells might be sentinels of the disease.
"More work is required to validate whether these changes are specific to AD, can be used to follow the course of AD or overlap with other neurodegenerative diseases involving inflammation," stated Dr. Cogswell. "However, the data highlight the potential of microRNAs to further understand sporadic Alzheimer's disease and provide accessible biomarkers to aid clinical diagnosis."
Dr. Cogswell, a former researcher at GlaxoSmithKline Inc., Research Triangle Park, NC, received his initial training from Duke University, Durham, North Carolina followed by postdoctoral fellowships in cellular and molecular immunology at the University of California, Los Angeles and University of North Carolina, Chapel Hill. In 16 years at GSK, Dr. Cogswell and colleagues developed high content qRT-PCR and histology applications that identified tractable targets from the human genome sequencing project and transcriptional biomarkers that decreased attrition in drug discovery.
Source:
Astrid Engelen
IOS Press
"My co-authors and I are extremely pleased to have been chosen by a distinguished group of our peers as the recipients of this year's Journal of Alzheimer's Disease award for our work on the use of biomarkers in the diagnosis of AD," said Dr. Cogswell.
Each year the Associate Editors of the Journal of Alzheimer's Disease select an outstanding article from the previous year's volume to receive this prestigious award, which is made possible by support from IOS Press and Elan Pharmaceuticals. Dr. Cogswell will be presented with the bronze Alzheimer Medal with the likeness of Alois Alzheimer and a cash award.
Dr. Cogswell's work examines changes in microRNA expression and their role in the sporadic form of the disease. MicroRNAs are small regulatory RNAs that affect many basic cellular and biological processes. They are best known for regulating RNA and protein expression in pathways and networks due to the combinatorial binding potential between microRNAs and their targets. Using a sensitive and specific qRT-PCR technology this paper demonstrates altered expression of specific microRNAs in the brain of Alzheimer's disease (AD) subjects. The changes were both dependent and independent of the pathological changes with some detected quite early in the disease. Many of the microRNAs have functional roles in known AD pathways including neuronal differentiation, glutamate, and innate immunity although the potential combinatorial effects on insulin signaling were noteworthy.
Because of the need for diagnostic biomarkers of disease progression this paper additionally examines the microRNAs in the cerebrospinal fluid of late stage AD patients. Again AD-specific changes were detected although here microRNAs with known and potential combinatorial effects on T lymphocyte signaling and inflammation pathways were identified. Because the CSF contains memory T cells and antigen presenting cells involved in immune-surveillance of the brain, these data suggested that microRNA responses in CSF cells might be sentinels of the disease.
"More work is required to validate whether these changes are specific to AD, can be used to follow the course of AD or overlap with other neurodegenerative diseases involving inflammation," stated Dr. Cogswell. "However, the data highlight the potential of microRNAs to further understand sporadic Alzheimer's disease and provide accessible biomarkers to aid clinical diagnosis."
Dr. Cogswell, a former researcher at GlaxoSmithKline Inc., Research Triangle Park, NC, received his initial training from Duke University, Durham, North Carolina followed by postdoctoral fellowships in cellular and molecular immunology at the University of California, Los Angeles and University of North Carolina, Chapel Hill. In 16 years at GSK, Dr. Cogswell and colleagues developed high content qRT-PCR and histology applications that identified tractable targets from the human genome sequencing project and transcriptional biomarkers that decreased attrition in drug discovery.
Source:
Astrid Engelen
IOS Press
Oregon Health & Science University Study Aims To Halt Alzheimer's By Blocking Enzyme
PORTLAND, Ore. - Oregon Health & Science University is participating in a national study of a drug that may prevent Alzheimer's disease by blocking an enzyme that produces plaques believed to trigger the disorder.
OHSU is one of six sites around the country taking part in a double-blind, placebo-controlled study of the agent known as LY450139, a gamma secretase inhibitor manufactured by Indianapolis-based Eli Lilly and Co. Other study sites are in Indianapolis, St. Louis, Philadelphia, Seattle, and La Jolla, Calif. Lilly is funding the study.
Gamma secretase is an enzyme that produces beta-amyloid by snipping a fragment of the protein from a larger protein that extends across the plasma membrane of the cell. The beta-amyloid fragments clump together to form dense, insoluble plaques inside the hippocampus, a curved, elongated ridge deep in the brain that controls learning and memory, and the cerebral cortex, the surface layer of gray matter of the cerebrum where sensory and motor information is coordinated.
The gamma secretase enzyme is made up of a complex of four proteins, and LY450139 is thought to de-activate it by binding within the complex, although the exact location is still being studied.
"There is a theory that beta-amyloid produces Alzheimer's disease, so if you stop the amyloid, you stop the disease," said Joseph Quinn, M.D., associate professor of neurology, and cell and developmental biology, OHSU School of Medicine and the Portland Veterans Affairs Medical Center. He also is an investigator at OHSU's Layton Aging & Alzheimer's Disease Center.
The study is "focused on the presumed underlying cause of the disease instead of symptoms. This is the beginning of the 'anti-amyloid' era of Alzheimer's disease treatment, attacking what are thought to be the roots of the disease," Quinn said.
The 29-week-long study, set for completion in September, is a Phase II trial involving 45 participants that will determine LY450139's safety, whether it causes any side effects, how much of the drug should be given and how long it can be detected in the blood. Researchers hope to measure levels of biomarkers in blood and spinal fluid that might relate to Alzheimer's disease, changes in the study subjects' thinking and memory, and changes in their daily living activities.
Study participants will be asked to make an initial office visit, followed by visits for treatments every other week for 14 weeks. They then will make two follow-up visits.
In a study co-authored by Quinn and published in the Feb. 28 issue of the journal Neurology, LY450139 was shown to reduce blood plasma levels of beta-amyloid by 38 percent in 70 Alzheimer's patients given 30 milligrams of LY450139 for one week, followed by 40 milligrams for five weeks. They reported that the lowest concentration of the protein occurred three hours after a 40 milligram dose was taken. The drug also was well tolerated.
"This study involved active treatment for only six weeks," Quinn said. "Clinical outcomes were not expected to change. This was the first step toward a trial intended to achieve clinical effects." OHSU was the largest recruiter for the study, enrolling 14 of the 70 participants.
A study published last summer in the journal Clinical Neuropharmacology found results similar to those in the Neurology study. In that Phase I trial, researchers saw a "dose-dependent" reduction blood plasma levels of beta-amyloid in 37 volunteers taking between 5 and 50 milligrams of LY450139 during a 14-day period. Side effects, which can include headache and abdominal pain, were manageable.
Eric Siemers, M.D., a neurologist at Eli Lilly and lead investigator for the Neurology and Clinical Neuropharmacology studies, said his company has been interested in finding therapies for Alzheimer's disease "for a number of years," and that LY450139 is "the first putative disease-modifying drug" to reach the clinical trial stage.
But that doesn't mean a therapy that will stop the cognitive decline caused by Alzheimer's disease is right around the corner, Siemers emphasized.
"The current study is primarily to look at tolerability, and also to confirm the biomarkers effects," he said. "Studies that look at clinical measures of cognitive decline in Alzheimer's disease patients typically require 12 to 18 months of treatment, and hundreds of subjects."
According to OHSU's Layton Aging and Alzheimer's Disease Center, 76,000 Oregonians are among an estimated 4.5 million Americans who have Alzheimer's disease, the most common form of dementia, or a related disorder. These dementias are especially common with increasing age and are expected to afflict half of those 85 and older in the coming years.
To access all OHSU news releases, visit ohsu/news/
Contact: Jonathan Modie
modiejohsu
Oregon Health & Science University
OHSU is one of six sites around the country taking part in a double-blind, placebo-controlled study of the agent known as LY450139, a gamma secretase inhibitor manufactured by Indianapolis-based Eli Lilly and Co. Other study sites are in Indianapolis, St. Louis, Philadelphia, Seattle, and La Jolla, Calif. Lilly is funding the study.
Gamma secretase is an enzyme that produces beta-amyloid by snipping a fragment of the protein from a larger protein that extends across the plasma membrane of the cell. The beta-amyloid fragments clump together to form dense, insoluble plaques inside the hippocampus, a curved, elongated ridge deep in the brain that controls learning and memory, and the cerebral cortex, the surface layer of gray matter of the cerebrum where sensory and motor information is coordinated.
The gamma secretase enzyme is made up of a complex of four proteins, and LY450139 is thought to de-activate it by binding within the complex, although the exact location is still being studied.
"There is a theory that beta-amyloid produces Alzheimer's disease, so if you stop the amyloid, you stop the disease," said Joseph Quinn, M.D., associate professor of neurology, and cell and developmental biology, OHSU School of Medicine and the Portland Veterans Affairs Medical Center. He also is an investigator at OHSU's Layton Aging & Alzheimer's Disease Center.
The study is "focused on the presumed underlying cause of the disease instead of symptoms. This is the beginning of the 'anti-amyloid' era of Alzheimer's disease treatment, attacking what are thought to be the roots of the disease," Quinn said.
The 29-week-long study, set for completion in September, is a Phase II trial involving 45 participants that will determine LY450139's safety, whether it causes any side effects, how much of the drug should be given and how long it can be detected in the blood. Researchers hope to measure levels of biomarkers in blood and spinal fluid that might relate to Alzheimer's disease, changes in the study subjects' thinking and memory, and changes in their daily living activities.
Study participants will be asked to make an initial office visit, followed by visits for treatments every other week for 14 weeks. They then will make two follow-up visits.
In a study co-authored by Quinn and published in the Feb. 28 issue of the journal Neurology, LY450139 was shown to reduce blood plasma levels of beta-amyloid by 38 percent in 70 Alzheimer's patients given 30 milligrams of LY450139 for one week, followed by 40 milligrams for five weeks. They reported that the lowest concentration of the protein occurred three hours after a 40 milligram dose was taken. The drug also was well tolerated.
"This study involved active treatment for only six weeks," Quinn said. "Clinical outcomes were not expected to change. This was the first step toward a trial intended to achieve clinical effects." OHSU was the largest recruiter for the study, enrolling 14 of the 70 participants.
A study published last summer in the journal Clinical Neuropharmacology found results similar to those in the Neurology study. In that Phase I trial, researchers saw a "dose-dependent" reduction blood plasma levels of beta-amyloid in 37 volunteers taking between 5 and 50 milligrams of LY450139 during a 14-day period. Side effects, which can include headache and abdominal pain, were manageable.
Eric Siemers, M.D., a neurologist at Eli Lilly and lead investigator for the Neurology and Clinical Neuropharmacology studies, said his company has been interested in finding therapies for Alzheimer's disease "for a number of years," and that LY450139 is "the first putative disease-modifying drug" to reach the clinical trial stage.
But that doesn't mean a therapy that will stop the cognitive decline caused by Alzheimer's disease is right around the corner, Siemers emphasized.
"The current study is primarily to look at tolerability, and also to confirm the biomarkers effects," he said. "Studies that look at clinical measures of cognitive decline in Alzheimer's disease patients typically require 12 to 18 months of treatment, and hundreds of subjects."
According to OHSU's Layton Aging and Alzheimer's Disease Center, 76,000 Oregonians are among an estimated 4.5 million Americans who have Alzheimer's disease, the most common form of dementia, or a related disorder. These dementias are especially common with increasing age and are expected to afflict half of those 85 and older in the coming years.
To access all OHSU news releases, visit ohsu/news/
Contact: Jonathan Modie
modiejohsu
Oregon Health & Science University
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