Saint Louis University researchers have identified a novel way of getting a potential treatment for Alzheimer's disease and stroke into the brain where it can do its work.
"We found a unique approach for delivering drugs to the brain," says William A. Banks, M.D., professor of geriatrics and pharmacological and physiological science at Saint Louis University. "We're turning off the guardian that's keeping the drugs out of the brain."
The brain is protected by the blood-brain barrier (BBB), a gate-keeping system of cells that lets in nutrients and keeps out foreign substances. The blood-brain barrier passes no judgment on which foreign substances are trying to get into the brain to treat diseases and which are trying to do harm, so it blocks them without discrimination.
"The problem in treating a lot of diseases of the central nervous system - such as Alzheimer's disease, HIV and stroke - is that we can't get drugs past the blood-brain barrier and into the brain," says Banks, who also is a staff physician at Veterans Affairs Medical Center in St. Louis.
"Our new research shows a way of getting a promising treatment for these types of devastating diseases to where they need to be to work."
The therapy - known as PACAP27 - is a hormone produced by the body that is a general neuro-protectant. PACAP stands for pituitary adenylate cyclase-activating polypeptide. "It is a general protector of the brain against many types of insult and injury," Banks says.
He compares a specific guarding mechanism in the BBB - efflux pumps - to bouncers at exclusive nightclubs. While they welcome those on the approved guest list, they look for trouble-makers trying to crash the party, refuse to let them in and evict them if they do get in.
The scientists isolated the particular gatekeeper than evicts PACAP27. Then they designed an antisense, a specific molecule that turned off the impediment.
"We went after the guard and essentially told him to go on break for a while so PACAP27 could get into the brain," Banks says.
They used mouse models of Alzheimer's disease and stroke to test what would happen if PACAP27 could get into the brain.
"We reversed the symptoms of the illnesses," Banks says. "The mice that had a version of Alzheimer's disease became smarter and in the stroke model, we reduced the amount of damage caused by the blockage of blood to the brain and improved brain recovery."
Simply turning off the gatekeeper that kept PACAP27 out of the brain allowed enough of the hormone that already is in the body to get inside the brain, where it effectively treated strokes. However, the mice that had a version of Alzheimer's disease needed both an extra dose of PACAP27 and the antisense that turned off the gatekeeper to improve learning.
"These findings are significant for three reasons. We have found a therapy that reverses symptoms of Alzheimers's disease and stroke in a mouse model. We have isolated the particular roadblock that keeps the treatment from getting into the brain. And we have found a way to finesse that obstacle so the medicine can get into the brain to do its work," Banks says. "This could have implications in treating many diseases of the central nervous system."
The findings were published in the Nov. 12 early online issue of the Journal of Cerebral Blood Flow & Metabolism.
Established in 1836, Saint Louis University School of Medicine has the distinction of awarding the first M.D. degree west of the Mississippi River. Saint Louis University School of Medicine is a pioneer in geriatric medicine, organ transplantation, chronic disease prevention, cardiovascular disease, neurosciences and vaccine research, among others. The School of Medicine trains physicians and biomedical scientists, conducts medical research, and provides health services on a local, national and international level.
Source: Nancy Solomon
Saint Louis University
воскресенье, 10 апреля 2011 г.
Proteins Anchor Memories In Our Brain
A University of Utah study suggests that memories are held in our brains because certain proteins serve as anchors, holding other proteins in place to strengthen synapses, which are connections between nerve cells.
"The essential idea is that synapses are in a constant state of flux, so how can they be the seat of memories that can last a lifetime?" says mathematics Professor Paul Bressloff, a member of the Brain Institute at the University of Utah. "Part of the answer is that there are anchors inside the synapse that keep proteins in place, and these proteins help determine how strong a synapse is, which in turn contributes to forming and retaining memories."
The research is relevant not only to how memory and learning work, but to Alzheimer's disease, which is believed to involve, at least in part, a breakdown in the normal movement of proteins within synapses.
The study was published Nov. 22, 2006, in The Journal of Neuroscience. Bressloff conducted the research with Berton Earnshaw, a doctoral student in mathematics. It was funded by the National Science Foundation.
Bressloff says the big debate about consciousness is, "Can it be explained simply in terms of a bunch of nerve impulses in the brain? In my opinion, the answer has to be yes" - an answer reinforced by his findings.
"Memories, behavior, feelings all are determined by patterns of nerve impulses in the brain," he adds. "If you change the pattern of nerve impulses, then that changes the memories, behavior and feelings. … What determines that pattern of nerve impulses is a mixture of stimuli we are receiving from the outside world and the strength of connections between nerve cells."
"Our knowledge and memories are determined by these connections in the brain. Who we are is determined by the strength of connections between neurons in the brain."
The Anatomy of Memory and Learning
A synapse is the junction between nerve cells or neurons. The synapse includes three parts: the end or "axon" of the upstream nerve cell, the microscopic gap between nerve cells, and a mushroom-shaped "dendritic spine," which is part of the downstream nerve cell.
What we learn and hold in our memory is believed to be distributed across many synapses, Bressloff says. Some memories, such as a person's face, may be held by just a few synapses, while other memories may be distributed across a large number, he adds.
While a nerve cell has only one axon to transmit outgoing signals, it has numerous structures called dendrites, which are like branches of a tree. Each dendrite, in turn, branches into twig-like dendritic spines. A single nerve cell may have 10,000 dendritic spines, and each spine is part of a synapse. So a single nerve cell can receive signals from 10,000 other nerve cells.
Nerve cells fire electric impulses. When an electrical nerve signal from one nerve cell arrives at the synapse, it triggers the release of chemicals called neurotransmitters. Those chemicals travel across the synapse and attach or "bind" to proteins on the dendritic spine that are called receptors.
One of the most important neurotransmitters is named glutamate, and it binds to proteins known as "AMPA receptors," which are embedded in the dendritic spines on the receiving end of nerve cells. The AMPA receptor proteins are held in the membrane by other proteins called "scaffolding proteins." Bressloff says AMPA is one of two key nerve-signal receptors known to "play a crucial role in learning and memory."
Earlier research indicates learning and memory depend on the strength of synapses between nerve cells. Bressloff says a synapse's strength depends not only on how much neurotransmitter is released by the upstream nerve cell, but on other factors, including the number of receptors like AMPA.
The Study: Simulating How Nerve Cells Receive Signals
Bressloff's study focused on how synapse strength relates to the number of AMPA receptors, which is crucial in determining how strong an electrical current is generated in a downstream nerve cell by a nerve impulse from an upstream nerve cell.
Individual AMPA receptors constantly are recycled or "trafficked" in and out of the synapse. So how can an ever-changing synapse help retain learning and memories?
Bressloff constructed a mathematical "model" - a simulation that used calculus equations to describe the movement of AMPA receptors in and out of the synapse.
The mathematical simulation was based on the notion that the downstream part of a synapse - namely, the mushroom-shaped dendritic spine - has two compartments. The first compartment looks like the cap of the mushroom. It is where AMPA receptors are held in place by scaffolding proteins so they can receive glutamate's chemical signal from the upstream nerve cell. The second compartment is like the mushroom's stalk.
Bressloff used 10 or fewer "differential equations" to describe four processes involved in determining the rates at which individual AMPA receptors leave or enter a synapse by moving between the cap- and stalk-like parts of the dendritic spine:
* Inside the cap, AMPA receptors can attach to scaffolding proteins so the receptors remain in place and can receive nerve signals via neurotransmitters.
* AMPA receptors that detach from scaffolding proteins can move back and forth between the cap and stalk; in other words, they can move in and out of the synapse.
* AMPA receptors can leave the dendritic spine completely, moving from the stalk to other parts of the dendrite that also are outside of the synapse. And they can move back into the stalk.
* AMPA receptors can leave the surface of the dendritic spine and move to its interior. And they can move back again.
* Bressloff tested his mathematical model against reality, showing the calculations accurately reflect how, over time, synapses become stronger as more nerve signals pass through them and weaker as fewer signals are transmitted.
That allowed him to ask what movements of AMPA receptors were likely to be responsible for making synapses stronger or weaker.
The simulation's answer: The strength of a synapse - and thus its ability to hold what we learn and remember - changes when there is a change in the number of scaffolding proteins that keep AMPA receptors in place in the synapse, specifically on the surface or cap of the mushroom-shaped dendritic spine.
In other words, the most important factor in strengthening synapses was the presence of scaffolding proteins that hold AMPA receptor proteins in place so they can receive nerve signals from neurotransmitter chemicals.
For synapses between nerves to grow stronger, "you can't just shove a bunch of new AMPA receptors to the surface because they will just go away again," Bressloff says. "You need to keep them there."
So what we remember and learn is, in effect, anchored to nerve cells in our brain.
"Our synapses are in a constant state of flux," Bressloff says. "They are exchanging molecules all the time. Yet we have stable memories and things we learn. So what is it that encodes a memory to the synapse if proteins are being changed all the time? Certain proteins act as anchors that keep other proteins in place."
Contacts:
Paul Bressloff, professor of mathematics
Lee Siegel
The University of Utah
The Brain Institute at the University of Utah
"The essential idea is that synapses are in a constant state of flux, so how can they be the seat of memories that can last a lifetime?" says mathematics Professor Paul Bressloff, a member of the Brain Institute at the University of Utah. "Part of the answer is that there are anchors inside the synapse that keep proteins in place, and these proteins help determine how strong a synapse is, which in turn contributes to forming and retaining memories."
The research is relevant not only to how memory and learning work, but to Alzheimer's disease, which is believed to involve, at least in part, a breakdown in the normal movement of proteins within synapses.
The study was published Nov. 22, 2006, in The Journal of Neuroscience. Bressloff conducted the research with Berton Earnshaw, a doctoral student in mathematics. It was funded by the National Science Foundation.
Bressloff says the big debate about consciousness is, "Can it be explained simply in terms of a bunch of nerve impulses in the brain? In my opinion, the answer has to be yes" - an answer reinforced by his findings.
"Memories, behavior, feelings all are determined by patterns of nerve impulses in the brain," he adds. "If you change the pattern of nerve impulses, then that changes the memories, behavior and feelings. … What determines that pattern of nerve impulses is a mixture of stimuli we are receiving from the outside world and the strength of connections between nerve cells."
"Our knowledge and memories are determined by these connections in the brain. Who we are is determined by the strength of connections between neurons in the brain."
The Anatomy of Memory and Learning
A synapse is the junction between nerve cells or neurons. The synapse includes three parts: the end or "axon" of the upstream nerve cell, the microscopic gap between nerve cells, and a mushroom-shaped "dendritic spine," which is part of the downstream nerve cell.
What we learn and hold in our memory is believed to be distributed across many synapses, Bressloff says. Some memories, such as a person's face, may be held by just a few synapses, while other memories may be distributed across a large number, he adds.
While a nerve cell has only one axon to transmit outgoing signals, it has numerous structures called dendrites, which are like branches of a tree. Each dendrite, in turn, branches into twig-like dendritic spines. A single nerve cell may have 10,000 dendritic spines, and each spine is part of a synapse. So a single nerve cell can receive signals from 10,000 other nerve cells.
Nerve cells fire electric impulses. When an electrical nerve signal from one nerve cell arrives at the synapse, it triggers the release of chemicals called neurotransmitters. Those chemicals travel across the synapse and attach or "bind" to proteins on the dendritic spine that are called receptors.
One of the most important neurotransmitters is named glutamate, and it binds to proteins known as "AMPA receptors," which are embedded in the dendritic spines on the receiving end of nerve cells. The AMPA receptor proteins are held in the membrane by other proteins called "scaffolding proteins." Bressloff says AMPA is one of two key nerve-signal receptors known to "play a crucial role in learning and memory."
Earlier research indicates learning and memory depend on the strength of synapses between nerve cells. Bressloff says a synapse's strength depends not only on how much neurotransmitter is released by the upstream nerve cell, but on other factors, including the number of receptors like AMPA.
The Study: Simulating How Nerve Cells Receive Signals
Bressloff's study focused on how synapse strength relates to the number of AMPA receptors, which is crucial in determining how strong an electrical current is generated in a downstream nerve cell by a nerve impulse from an upstream nerve cell.
Individual AMPA receptors constantly are recycled or "trafficked" in and out of the synapse. So how can an ever-changing synapse help retain learning and memories?
Bressloff constructed a mathematical "model" - a simulation that used calculus equations to describe the movement of AMPA receptors in and out of the synapse.
The mathematical simulation was based on the notion that the downstream part of a synapse - namely, the mushroom-shaped dendritic spine - has two compartments. The first compartment looks like the cap of the mushroom. It is where AMPA receptors are held in place by scaffolding proteins so they can receive glutamate's chemical signal from the upstream nerve cell. The second compartment is like the mushroom's stalk.
Bressloff used 10 or fewer "differential equations" to describe four processes involved in determining the rates at which individual AMPA receptors leave or enter a synapse by moving between the cap- and stalk-like parts of the dendritic spine:
* Inside the cap, AMPA receptors can attach to scaffolding proteins so the receptors remain in place and can receive nerve signals via neurotransmitters.
* AMPA receptors that detach from scaffolding proteins can move back and forth between the cap and stalk; in other words, they can move in and out of the synapse.
* AMPA receptors can leave the dendritic spine completely, moving from the stalk to other parts of the dendrite that also are outside of the synapse. And they can move back into the stalk.
* AMPA receptors can leave the surface of the dendritic spine and move to its interior. And they can move back again.
* Bressloff tested his mathematical model against reality, showing the calculations accurately reflect how, over time, synapses become stronger as more nerve signals pass through them and weaker as fewer signals are transmitted.
That allowed him to ask what movements of AMPA receptors were likely to be responsible for making synapses stronger or weaker.
The simulation's answer: The strength of a synapse - and thus its ability to hold what we learn and remember - changes when there is a change in the number of scaffolding proteins that keep AMPA receptors in place in the synapse, specifically on the surface or cap of the mushroom-shaped dendritic spine.
In other words, the most important factor in strengthening synapses was the presence of scaffolding proteins that hold AMPA receptor proteins in place so they can receive nerve signals from neurotransmitter chemicals.
For synapses between nerves to grow stronger, "you can't just shove a bunch of new AMPA receptors to the surface because they will just go away again," Bressloff says. "You need to keep them there."
So what we remember and learn is, in effect, anchored to nerve cells in our brain.
"Our synapses are in a constant state of flux," Bressloff says. "They are exchanging molecules all the time. Yet we have stable memories and things we learn. So what is it that encodes a memory to the synapse if proteins are being changed all the time? Certain proteins act as anchors that keep other proteins in place."
Contacts:
Paul Bressloff, professor of mathematics
Lee Siegel
The University of Utah
The Brain Institute at the University of Utah
Potential Alzheimer's Treatment From The Humble Potato
A virus that commonly infects potatoes bears a striking resemblance to one of the key proteins implicated in Alzheimer's disease (AD), and researchers have used that to develop antibodies that may slow or prevent the onset of AD.
Studies in mice have demonstrated that vaccinations with the amyloid beta protein (believed to be a major AD contributor) to produce A' antibodies can slow disease progression and improve cognitive function, possibly by promoting the destruction of amyloid plaques. Some early human trials have likewise been promising, but had to be halted due to the risk of autoimmune encephalitis.
One way to make Alzheimer's vaccinations safer would be to use a closely-related, but not human, protein as the vaccine, much like cowpox virus is used for smallpox immunizations.
In the Journal of Biological Chemistry, Robert Friedland and colleagues used this concept on an amyloid-like protein found in potato virus (PVY). They injected PVY into mice followed by monthly boosters for four months. The researchers found that the mice produced strong levels of antibodies that could attach to amyloid beta protein both in both solution and in tissue samples of Alzheimer's patients. And although the levels were lower, mice also developed A?? antibodies if given injections of PVY-infected potato leaf as opposed to purified PVY.
Friedland and colleagues note that potato virus is a fairly common infection that poses no risk to humans (many people have probably eaten PVY infected potatoes). While tests of PVY antibodies will ultimately determine how useful they can be, they may be a promising lead to treating this debilitating disease.
From the JBC article: "Antibodies to Potato Virus Y Bind the Amyloid Beta Peptide" by Robert P. Friedland, Jonathan M. Tedesco, Andrea Wilson, Craig Atwood, Mark Smith, George Perry and Michael Zagorski.
Article Link
Author: Robert P. Friedland, Department of Neurology, Case Western Reserve University School of Medicine, Clevelland, OH.
The American Society for Biochemistry and Molecular Biology is a nonprofit scientific and educational organization with over 11,900 members in the United States and internationally. Most members teach and conduct research at colleges and universities. Others conduct research in various government laboratories, nonprofit research institutions and industry. The Society's student members attend undergraduate or graduate institutions.
Founded in 1906, the Society is based in Bethesda, Maryland, on the campus of the Federation of American Societies for Experimental Biology. The Society's purpose is to advance the science of biochemistry and molecular biology through publication of the Journal of Biological Chemistry, the Journal of Lipid Research, and Molecular and Cellular Proteomics, organization of scientific meetings, advocacy for funding of basic research and education, support of science education at all levels, and promoting the diversity of individuals entering the scientific work force.
For more information about ASBMB, see the Society's Web site at asbmb/.
Source: Nick Zagorski
American Society for Biochemistry and Molecular Biology
Studies in mice have demonstrated that vaccinations with the amyloid beta protein (believed to be a major AD contributor) to produce A' antibodies can slow disease progression and improve cognitive function, possibly by promoting the destruction of amyloid plaques. Some early human trials have likewise been promising, but had to be halted due to the risk of autoimmune encephalitis.
One way to make Alzheimer's vaccinations safer would be to use a closely-related, but not human, protein as the vaccine, much like cowpox virus is used for smallpox immunizations.
In the Journal of Biological Chemistry, Robert Friedland and colleagues used this concept on an amyloid-like protein found in potato virus (PVY). They injected PVY into mice followed by monthly boosters for four months. The researchers found that the mice produced strong levels of antibodies that could attach to amyloid beta protein both in both solution and in tissue samples of Alzheimer's patients. And although the levels were lower, mice also developed A?? antibodies if given injections of PVY-infected potato leaf as opposed to purified PVY.
Friedland and colleagues note that potato virus is a fairly common infection that poses no risk to humans (many people have probably eaten PVY infected potatoes). While tests of PVY antibodies will ultimately determine how useful they can be, they may be a promising lead to treating this debilitating disease.
From the JBC article: "Antibodies to Potato Virus Y Bind the Amyloid Beta Peptide" by Robert P. Friedland, Jonathan M. Tedesco, Andrea Wilson, Craig Atwood, Mark Smith, George Perry and Michael Zagorski.
Article Link
Author: Robert P. Friedland, Department of Neurology, Case Western Reserve University School of Medicine, Clevelland, OH.
The American Society for Biochemistry and Molecular Biology is a nonprofit scientific and educational organization with over 11,900 members in the United States and internationally. Most members teach and conduct research at colleges and universities. Others conduct research in various government laboratories, nonprofit research institutions and industry. The Society's student members attend undergraduate or graduate institutions.
Founded in 1906, the Society is based in Bethesda, Maryland, on the campus of the Federation of American Societies for Experimental Biology. The Society's purpose is to advance the science of biochemistry and molecular biology through publication of the Journal of Biological Chemistry, the Journal of Lipid Research, and Molecular and Cellular Proteomics, organization of scientific meetings, advocacy for funding of basic research and education, support of science education at all levels, and promoting the diversity of individuals entering the scientific work force.
For more information about ASBMB, see the Society's Web site at asbmb/.
Source: Nick Zagorski
American Society for Biochemistry and Molecular Biology
Events Seek To Raise Health Awareness Among Blacks; Magazine Ranks Top Schools For Hispanic Medical Students
The following summarizes events related to reducing racial health care disparities.
Portland, Ore.: Portland Community College's Cascade Campus on Saturday will host a conference that focuses on memory and aging in the black community, the Oregonian reports. The conference, "Hold on to Your Memory," will offer health screenings to participants and address stroke, diabetes and other blood vessel conditions that can cause vascular dementia, Linda Boise, director of education at the Layton Aging & Alzheimer's Disease Center at Oregon Health & Sciences University, said (Dworkin, Oregonian, 9/3).
University of California-Davis: Hispanic Business Magazine has ranked UC-Davis' School of Medicine among the top 10 medical schools in the nation for Hispanic students, the Sacramento Bee reports. The ranking is based on enrollment, retention, reputation, faculty and student services. The magazine said the school is committed to training a physician work force that meets the diverse demands of California (Lindelof, Sacramento Bee, 9/3). The list of medical schools in the top 10 is available online.
Winston-Salem State University: WSSU on Saturday will host the Women's Health Symposium, which aims to educate women on how to lead healthier lifestyles, reduce obesity and address other chronic health conditions, the Winston-Salem Chronicle reports. The event is being sponsored by the BET Foundation, General Mills' Honey Nut Cheerios, WSSU's Center of Excellence for the Elimination of Health Disparities and Wake Forest University School of Medicine's Maya Angelou Research Center on Minority Health. Fitness classes, cooking demonstrations, health screenings, panel discussions, health exhibits and workshops with health professionals will be included in the event (Winston-Salem Chronicle, 9/3).
Reprinted with kind permission from kaisernetwork. You can view the entire Kaiser Daily Health Policy Report, search the archives, or sign up for email delivery at kaisernetwork/dailyreports/healthpolicy. The Kaiser Daily Health Policy Report is published for kaisernetwork, a free service of The Henry J. Kaiser Family Foundation.
© 2008 Advisory Board Company and Kaiser Family Foundation. All rights reserved.
Portland, Ore.: Portland Community College's Cascade Campus on Saturday will host a conference that focuses on memory and aging in the black community, the Oregonian reports. The conference, "Hold on to Your Memory," will offer health screenings to participants and address stroke, diabetes and other blood vessel conditions that can cause vascular dementia, Linda Boise, director of education at the Layton Aging & Alzheimer's Disease Center at Oregon Health & Sciences University, said (Dworkin, Oregonian, 9/3).
University of California-Davis: Hispanic Business Magazine has ranked UC-Davis' School of Medicine among the top 10 medical schools in the nation for Hispanic students, the Sacramento Bee reports. The ranking is based on enrollment, retention, reputation, faculty and student services. The magazine said the school is committed to training a physician work force that meets the diverse demands of California (Lindelof, Sacramento Bee, 9/3). The list of medical schools in the top 10 is available online.
Winston-Salem State University: WSSU on Saturday will host the Women's Health Symposium, which aims to educate women on how to lead healthier lifestyles, reduce obesity and address other chronic health conditions, the Winston-Salem Chronicle reports. The event is being sponsored by the BET Foundation, General Mills' Honey Nut Cheerios, WSSU's Center of Excellence for the Elimination of Health Disparities and Wake Forest University School of Medicine's Maya Angelou Research Center on Minority Health. Fitness classes, cooking demonstrations, health screenings, panel discussions, health exhibits and workshops with health professionals will be included in the event (Winston-Salem Chronicle, 9/3).
Reprinted with kind permission from kaisernetwork. You can view the entire Kaiser Daily Health Policy Report, search the archives, or sign up for email delivery at kaisernetwork/dailyreports/healthpolicy. The Kaiser Daily Health Policy Report is published for kaisernetwork, a free service of The Henry J. Kaiser Family Foundation.
© 2008 Advisory Board Company and Kaiser Family Foundation. All rights reserved.
UK Heading Towards A 'Silent Epidemic' Of Alcohol-Related Dementia - Royal College Of Psychiatrists
Urgent action is needed to prevent a 'silent epidemic' of alcohol-related dementia in the UK, psychiatrists have warned.
Writing in the November issue of the British Journal of Psychiatry, two London-based psychiatrists with a special interest in dementia discuss the potential impact of increasing alcohol consumption among young and middle-aged people.
Dr Susham Gupta, a specialist registrar in adult and old age psychiatry, and Dr James Warner, a consultant in older adults' psychiatry, observe that attitudes towards alcohol have changed significantly over the last few decades. Not only has society taken a more relaxed attitude to drinking, but alcohol has become cheaper and more widely available.
The price of alcohol relative to average UK income has halved since the 1960s, while per capita consumption of alcohol has nearly doubled from less than six litres a year in the early 1960s to over 11.5 litres per year in 2000. If this trend continues, the UK will become Europe's biggest per capita consumer of alcohol within a decade.
Previous research has shown that excessive alcohol consumption can lead to loss of brain tissue, and that binge drinking is associated with an increased risk of dementia.
Given the neurotoxic effects of alcohol - and the seemingly inexorable rise in heavy drinking - the authors of the paper conclude that we are likely to see a surge in cases of alcohol-related dementia in future generations.
This problem may be compounded by the fact that more people are using recreational drugs such as ecstasy, whose long-term effects on the brain are still unclear.
Dr Gupta and Dr Warner describe alcohol-related dementia as an "under-recognised problem", and call for the development of new tools to help doctors assess the risks of alcohol-related cognitive impairment.
Better public education about heavy drinking and the risk of developing dementia is also needed, although Dr Gupta and Dr Warner acknowledge that awareness campaigns may be both "unpopular and ineffective". "This might need similar legislation to that used in the fight against tobacco-related health problems," they conclude.
Reference
"Alcohol-related dementia: a 21st-century silent epidemic?"
Gupta S and Warner J (2008)
British Journal of Psychiatry, 193: 351-353
The Royal College of Psychiatrists
The Royal College of Psychiatrists is the professional and educational body for psychiatrists in the United Kingdom and the Republic of Ireland. We promote mental health by:
-- Setting standards and promoting excellence in mental health care
-- Improving understanding through research and education
-- Leading, representing, training and supporting psychiatrists
-- Working with patients, carers and their organisations
As well as running its membership examination (MRCPsych), and visiting and approving hospitals for training purposes, the College organises scientific and clinical conferences and lectures and continuing professional development activities. The College publishes books, reports and educational material for professionals and the general public. It also publishes the British Journal of Psychiatry , Psychiatric Bulletin , Advances in Psychiatric Treatment and International Psychiatry , all of which are now available on-line.
The Royal College of Psychiatrists has been in existence in some form since 1841. First as the "Association of Medical Officers of Asylums and Hospitals for the Insane" (later changed to the Medico Psychological Association) then, in 1926 receiving its Royal Charter to become the "Royal Medico Psychological Association, and finally, in 1971 receiving a Supplemental Charter to become the "Royal College of Psychiatrists" we know today.
Royal College of Psychiatrists
Writing in the November issue of the British Journal of Psychiatry, two London-based psychiatrists with a special interest in dementia discuss the potential impact of increasing alcohol consumption among young and middle-aged people.
Dr Susham Gupta, a specialist registrar in adult and old age psychiatry, and Dr James Warner, a consultant in older adults' psychiatry, observe that attitudes towards alcohol have changed significantly over the last few decades. Not only has society taken a more relaxed attitude to drinking, but alcohol has become cheaper and more widely available.
The price of alcohol relative to average UK income has halved since the 1960s, while per capita consumption of alcohol has nearly doubled from less than six litres a year in the early 1960s to over 11.5 litres per year in 2000. If this trend continues, the UK will become Europe's biggest per capita consumer of alcohol within a decade.
Previous research has shown that excessive alcohol consumption can lead to loss of brain tissue, and that binge drinking is associated with an increased risk of dementia.
Given the neurotoxic effects of alcohol - and the seemingly inexorable rise in heavy drinking - the authors of the paper conclude that we are likely to see a surge in cases of alcohol-related dementia in future generations.
This problem may be compounded by the fact that more people are using recreational drugs such as ecstasy, whose long-term effects on the brain are still unclear.
Dr Gupta and Dr Warner describe alcohol-related dementia as an "under-recognised problem", and call for the development of new tools to help doctors assess the risks of alcohol-related cognitive impairment.
Better public education about heavy drinking and the risk of developing dementia is also needed, although Dr Gupta and Dr Warner acknowledge that awareness campaigns may be both "unpopular and ineffective". "This might need similar legislation to that used in the fight against tobacco-related health problems," they conclude.
Reference
"Alcohol-related dementia: a 21st-century silent epidemic?"
Gupta S and Warner J (2008)
British Journal of Psychiatry, 193: 351-353
The Royal College of Psychiatrists
The Royal College of Psychiatrists is the professional and educational body for psychiatrists in the United Kingdom and the Republic of Ireland. We promote mental health by:
-- Setting standards and promoting excellence in mental health care
-- Improving understanding through research and education
-- Leading, representing, training and supporting psychiatrists
-- Working with patients, carers and their organisations
As well as running its membership examination (MRCPsych), and visiting and approving hospitals for training purposes, the College organises scientific and clinical conferences and lectures and continuing professional development activities. The College publishes books, reports and educational material for professionals and the general public. It also publishes the British Journal of Psychiatry , Psychiatric Bulletin , Advances in Psychiatric Treatment and International Psychiatry , all of which are now available on-line.
The Royal College of Psychiatrists has been in existence in some form since 1841. First as the "Association of Medical Officers of Asylums and Hospitals for the Insane" (later changed to the Medico Psychological Association) then, in 1926 receiving its Royal Charter to become the "Royal Medico Psychological Association, and finally, in 1971 receiving a Supplemental Charter to become the "Royal College of Psychiatrists" we know today.
Royal College of Psychiatrists
Variant prion protein causes infection but no symptoms - Could have implications for Alzheimer's disease
Abnormal prion proteins are little understood disease agents involved in causing horrific brain-wasting diseases such as
Creutzfeldt-Jacob disease in people, mad cow disease in cattle and chronic wasting disease in deer and elk. Now, new research
suggests that a variant form of abnormal prion protein--one lacking an "anchor" into the cell membrane--may be unable to
signal cells to start the lethal disease process, according to scientists at the Rocky Mountain Laboratories (RML), part of
the National Institute of Allergy and Infectious Diseases (NIAID) of the National Institutes of Health.
"This work provides novel insights into how prion and other neurodegenerative diseases develop and it provides tantalizing
clues as to how we might delay or even prevent such diseases by preventing certain cellular interactions," notes NIAID
Director Anthony S. Fauci, M.D. A paper describing the research was released online today by the journal Science. RML
virologist Bruce Chesebro, M.D., directed the project. Other key co-authors from the Hamilton, MT, RML laboratory include
Richard Race, D.V.M., and Gerald Baron, Ph.D. Their collaborators included Michael Oldstone, M.D., and Matthew Trifilo,
Ph.D., of The Scripps Research Institute in La Jolla, CA, and Eliezer Masliah, M.D., of the University of California, San
Diego (UCSD).
Drawing on experimental concepts first developed at RML a decade ago, the research team exposed two groups of 6-week-old mice
to different strains of the agent that causes scrapie, a brain-wasting disease of sheep. Within 150 days of being inoculated
with the natural form of scrapie prion protein, all 70 mice in the control group showed visible signs of infection:
twitching, emaciation and poor coordination. In contrast, the scientists observed 128 transgenic mice--those engineered to
produce prion protein without a glycophosphoinositol (GPI) cell membrane anchor--for 500 to 600 days and saw no signs of
scrapie disease. Subsequent electron microscopic examinations at UCSD, however, confirmed that they produced amyloid fibrils,
an abnormal form of prion protein, and that they even had brain lesions. More remarkably, according to Dr. Chesebro, the
diseased brain tissue resembled that found in Alzheimer's disease rather than in scrapie.
Chesebro mentions two theories as to why the transgenic mice did not show symptoms of illness despite being infected:
-- The host cell might require the GPI anchor to receive the "toxic signal" from the abnormal prion protein
-- The plaques might be less toxic than the non-plaque form of prion protein clumps
In either case, more time might be required to produce disease due to the reduced toxicity, Dr. Chesebro says.
"There was so much about this research that surprised us and gave us ideas to pursue," says Dr. Chesebro. "First, the mice
didn't get sick. That's very significant. Second, the dense accumulations of scrapie plaque in the brain resembled the plaque
seen in Alzheimer's, but it wasn't toxic," which might support more recent concepts about plaque in Alzheimer's patients.
"Previously, most researchers thought plaques were the toxic component of Alzheimer's that kills neurons, and many treatments
focus on removing the plaques. But what if the plaques are inert, as they were in this research? What if only small clumps
are toxic?"
If this hypothesis proves correct, Dr. Chesebro says, the ongoing research could eventually alter scientists' views on
preventing prion diseases, shifting emphasis away from stopping the production of prion protein clumps and toward preventing
interactions with prion protein anchored to cells, or learning to direct abnormal prion protein accumulations to specific
parts of the brain where they will not produce symptoms.
"Abnormal prion protein by itself may not be rapidly lethal--in these mice it wasn't," Dr. Chesebro says.
NIAID is a component of the National Institutes of Health, an agency of the U.S. Department of Health and Human Services.
NIAID supports basic and applied research to prevent, diagnose and treat infectious diseases such as HIV/AIDS and other
sexually transmitted infections, influenza, tuberculosis, malaria and illness from potential agents of bioterrorism. NIAID
also supports research on transplantation and immune-related illnesses, including autoimmune disorders, asthma and allergies.
Reference: B Chesebro et al. Anchorless prion protein results in infectious amyloid disease without clinical scrapie. Science
308 (5727):1435-39 (2005). DOI: 10.1126/science.1110837.
News releases, fact sheets and other NIAID-related materials are available on the NIAID Web site at niaid.nih.
Contact: Ken Pekoc
kpekocniaid.nih
406-375-9690
NIH/National Institute of Allergy and Infectious Diseases
niaid.nih
Creutzfeldt-Jacob disease in people, mad cow disease in cattle and chronic wasting disease in deer and elk. Now, new research
suggests that a variant form of abnormal prion protein--one lacking an "anchor" into the cell membrane--may be unable to
signal cells to start the lethal disease process, according to scientists at the Rocky Mountain Laboratories (RML), part of
the National Institute of Allergy and Infectious Diseases (NIAID) of the National Institutes of Health.
"This work provides novel insights into how prion and other neurodegenerative diseases develop and it provides tantalizing
clues as to how we might delay or even prevent such diseases by preventing certain cellular interactions," notes NIAID
Director Anthony S. Fauci, M.D. A paper describing the research was released online today by the journal Science. RML
virologist Bruce Chesebro, M.D., directed the project. Other key co-authors from the Hamilton, MT, RML laboratory include
Richard Race, D.V.M., and Gerald Baron, Ph.D. Their collaborators included Michael Oldstone, M.D., and Matthew Trifilo,
Ph.D., of The Scripps Research Institute in La Jolla, CA, and Eliezer Masliah, M.D., of the University of California, San
Diego (UCSD).
Drawing on experimental concepts first developed at RML a decade ago, the research team exposed two groups of 6-week-old mice
to different strains of the agent that causes scrapie, a brain-wasting disease of sheep. Within 150 days of being inoculated
with the natural form of scrapie prion protein, all 70 mice in the control group showed visible signs of infection:
twitching, emaciation and poor coordination. In contrast, the scientists observed 128 transgenic mice--those engineered to
produce prion protein without a glycophosphoinositol (GPI) cell membrane anchor--for 500 to 600 days and saw no signs of
scrapie disease. Subsequent electron microscopic examinations at UCSD, however, confirmed that they produced amyloid fibrils,
an abnormal form of prion protein, and that they even had brain lesions. More remarkably, according to Dr. Chesebro, the
diseased brain tissue resembled that found in Alzheimer's disease rather than in scrapie.
Chesebro mentions two theories as to why the transgenic mice did not show symptoms of illness despite being infected:
-- The host cell might require the GPI anchor to receive the "toxic signal" from the abnormal prion protein
-- The plaques might be less toxic than the non-plaque form of prion protein clumps
In either case, more time might be required to produce disease due to the reduced toxicity, Dr. Chesebro says.
"There was so much about this research that surprised us and gave us ideas to pursue," says Dr. Chesebro. "First, the mice
didn't get sick. That's very significant. Second, the dense accumulations of scrapie plaque in the brain resembled the plaque
seen in Alzheimer's, but it wasn't toxic," which might support more recent concepts about plaque in Alzheimer's patients.
"Previously, most researchers thought plaques were the toxic component of Alzheimer's that kills neurons, and many treatments
focus on removing the plaques. But what if the plaques are inert, as they were in this research? What if only small clumps
are toxic?"
If this hypothesis proves correct, Dr. Chesebro says, the ongoing research could eventually alter scientists' views on
preventing prion diseases, shifting emphasis away from stopping the production of prion protein clumps and toward preventing
interactions with prion protein anchored to cells, or learning to direct abnormal prion protein accumulations to specific
parts of the brain where they will not produce symptoms.
"Abnormal prion protein by itself may not be rapidly lethal--in these mice it wasn't," Dr. Chesebro says.
NIAID is a component of the National Institutes of Health, an agency of the U.S. Department of Health and Human Services.
NIAID supports basic and applied research to prevent, diagnose and treat infectious diseases such as HIV/AIDS and other
sexually transmitted infections, influenza, tuberculosis, malaria and illness from potential agents of bioterrorism. NIAID
also supports research on transplantation and immune-related illnesses, including autoimmune disorders, asthma and allergies.
Reference: B Chesebro et al. Anchorless prion protein results in infectious amyloid disease without clinical scrapie. Science
308 (5727):1435-39 (2005). DOI: 10.1126/science.1110837.
News releases, fact sheets and other NIAID-related materials are available on the NIAID Web site at niaid.nih.
Contact: Ken Pekoc
kpekocniaid.nih
406-375-9690
NIH/National Institute of Allergy and Infectious Diseases
niaid.nih
Latinos And African Americans Live Longer With Alzheimer's Disease
Latinos and African Americans with Alzheimer's disease live longer than white people who have the disease, according to a study published November 14, 2007, in the online edition of Neurology®, the medical journal of the American Academy of Neurology.
The findings were the same even after researchers adjusted for education level, age when symptoms began, living situation, and other factors that could affect how long the study participants lived. Autopsies showed that the severity of the disease was similar among the ethnicities.
The study involved nearly 31,000 people with Alzheimer's who were seen at Alzheimer's Disease Centers across the country. Of the participants, 81 percent were white, 12 percent were African American, four percent were Latino, 1.5 percent were Asian and .5 percent were American Indian. They were followed for an average of 2.4 years. The participants lived for an average of 4.8 years after being diagnosed with the disease. Autopsies were performed on 3,000 of the participants.
Latino participants lived an average of about 40 percent longer than the white participants; African American participants lived an average of 15 percent longer than whites did. Asian and American Indian participants lived about as long with the disease as the white participants did.
"It's not clear why Latinos and African Americans have an advantage when it comes to living longer with Alzheimer's disease," said study author Kala Mehta, DSc, of the University of California, San Francisco, and member of the American Academy of Neurology. "Possible explanations may be underlying genetic or cultural factors."
Mehta said other factors that could account for the differences in surviving with the disease could be varying levels of social support from extended family, varying levels of health and diseases in addition to Alzheimer's disease, varying levels of treatment of other diseases, and differences in measurement or earlier diagnosis in some groups. Another factor could be length of stay in the United States; many participants came from other countries where the survival time with Alzheimer's may differ from in the United States.
"Determining the underlying factors behind this difference could lead to longer survival for everyone with Alzheimer's disease," Mehta said. "Regardless of the reason for this difference, these findings may have implications for health care planning for people with Alzheimer's disease."
Mehta says no general conclusions should be drawn about the inherent health or fitness of the ethnic groups involved.
The study was supported by grants from the National Institute on Aging and the National Alzheimer's Coordinating Center.
The American Academy of Neurology, an association of more than 20,000 neurologists and neuroscience professionals, is dedicated to improving patient care through education and research. A neurologist is a doctor with specialized training in diagnosing, treating and managing disorders of the brain and nervous system such as stroke, Alzheimer's disease, epilepsy, Parkinson's disease, and multiple sclerosis.
For more information about the American Academy of Neurology, visit aan.
American Academy of Neurology (AAN)
1080 Montreal Ave.
St. Paul, MN 55116
United States
neurology
The findings were the same even after researchers adjusted for education level, age when symptoms began, living situation, and other factors that could affect how long the study participants lived. Autopsies showed that the severity of the disease was similar among the ethnicities.
The study involved nearly 31,000 people with Alzheimer's who were seen at Alzheimer's Disease Centers across the country. Of the participants, 81 percent were white, 12 percent were African American, four percent were Latino, 1.5 percent were Asian and .5 percent were American Indian. They were followed for an average of 2.4 years. The participants lived for an average of 4.8 years after being diagnosed with the disease. Autopsies were performed on 3,000 of the participants.
Latino participants lived an average of about 40 percent longer than the white participants; African American participants lived an average of 15 percent longer than whites did. Asian and American Indian participants lived about as long with the disease as the white participants did.
"It's not clear why Latinos and African Americans have an advantage when it comes to living longer with Alzheimer's disease," said study author Kala Mehta, DSc, of the University of California, San Francisco, and member of the American Academy of Neurology. "Possible explanations may be underlying genetic or cultural factors."
Mehta said other factors that could account for the differences in surviving with the disease could be varying levels of social support from extended family, varying levels of health and diseases in addition to Alzheimer's disease, varying levels of treatment of other diseases, and differences in measurement or earlier diagnosis in some groups. Another factor could be length of stay in the United States; many participants came from other countries where the survival time with Alzheimer's may differ from in the United States.
"Determining the underlying factors behind this difference could lead to longer survival for everyone with Alzheimer's disease," Mehta said. "Regardless of the reason for this difference, these findings may have implications for health care planning for people with Alzheimer's disease."
Mehta says no general conclusions should be drawn about the inherent health or fitness of the ethnic groups involved.
The study was supported by grants from the National Institute on Aging and the National Alzheimer's Coordinating Center.
The American Academy of Neurology, an association of more than 20,000 neurologists and neuroscience professionals, is dedicated to improving patient care through education and research. A neurologist is a doctor with specialized training in diagnosing, treating and managing disorders of the brain and nervous system such as stroke, Alzheimer's disease, epilepsy, Parkinson's disease, and multiple sclerosis.
For more information about the American Academy of Neurology, visit aan.
American Academy of Neurology (AAN)
1080 Montreal Ave.
St. Paul, MN 55116
United States
neurology
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