Women at the Center of the Global Alzheimer's Epidemic
- Five-Country Survey and Women & Alzheimer's Panel -
- Highlight the Unique Impact of Alzheimer's on Women -
PARIS, July 18, 2011 – Today the Alzheimer's Association® in conjunction with GE Healthcare held a "Women and Alzheimer's: A Global Perspective" panel discussion during the Alzheimer's Association International Conference 2011 (AAIC). The event brought together leaders in the Alzheimer's field and revealed new data from "The Value of Knowing Survey" (Survey) commissioned by Alzheimer's Europe and administered by Harvard School of Public Health. The findings explored the impact of Alzheimer's disease on women and highlighted some of the different perspectives women have about the disease compared to men in France, Germany, Spain, Poland and the United States.
36.5 million people worldwide are estimated to be living with dementia. The new data from the multi-country survey revealed:
- In all countries women were more fearful of getting Alzheimer's compared to other diseases, second only to cancer and women in France were 15 percent more afraid of developing Alzheimer's than their male counterparts.
- Likewise, women in all five countries were more concerned than men about a loved one developing Alzheimer's.
- Almost 60 percent of women in the United States and nearly 50 percent of women in France were aware that Alzheimer's is a progressive and fatal disease.
- Women in all countries, the highest being 90 percent of women in Spain, believed that government spending on Alzheimer's research should be increased, the lowest being nearly 70 percent of women in Germany.
- Women in all countries were more likely than their male counterparts to be involved in day-to-day care. In Poland there was more than a 10 percent differential.
- In addition to providing the day-to-day care, women in France and Poland were significantly more involved in the decision-making and financial support of the person living with Alzheimer's disease.
- Should men or women develop Alzheimer's, the largest percentage of respondents identified their spouse as the person who would be responsible for their primary care, with men identifying their wives 6-18 percent more often than wives identifying their husbands. In Spain there was an 18 percent difference. Also of interest was that women were more likely to rely on children or paid caregivers outside the family than men.
- Despite the fear of the disease and the fact that women are more often caregivers, women in France and the United States appear to be more optimistic that an effective treatment for Alzheimer's will be developed in the next five years, 71 and 76 percent respectively.
"With statistics consistently pointing to the fact that more women are living with Alzheimer's and caring for people with Alzheimer's, it is clear women are disproportionately affected by this disease," said Angela Geiger, Chief Strategy Officer of the Alzheimer's Association. "These insights reinforce the conclusions published in The Shriver Report: A Women's Nation Takes on Alzheimer's which found the impact of Alzheimer's on women is significant. The perspectives we see in this survey must prompt thoughtful conversations about Alzheimer's with our friends, family members and government officials to change the trajectory of Alzheimer's disease."
"The data pointing to the number of people living with Alzheimer's and the impact on those providing care is enormous, translating into overwhelming human and financial costs," Pascale Witz, president and CEO for GE Healthcare's Medical Diagnostics business. "At GE Healthcare we are driving innovation in the industry by focusing our efforts in Alzheimer's disease on earlier diagnosis, with research into new imaging compounds, new technologies and biomarkers. With early diagnosis comes earlier treatment and the potential for delays in disease progression.
AHAF-Supported Researchers Discover How ApoE4 Contributes To Alzheimer’s Plaques
Malfunctioning protein slows the brain’s ability to “clear out” toxic beta-amyloid
June 30, 2011
“More and more, breaking news reflects AHAF’s significant effort to end Alzheimer’s disease,” says AHAF President and CEO Stacy Pagos Haller. “Our tradition of funding early-stage, innovative projects results in important discoveries like the one announced in this latest Alzheimer's disease news update. See how our grants are making a difference.”
People with a particular variation of the apolipoprotein E (ApoE) gene, called ApoE4, have a strong risk of developing late-onset Alzheimer's disease. ApoE4 protein helps to metabolize cholesterol, but how it causes an increased risk for Alzheimer's is unknown.
In the June 29 issue of the journal Science Translational Medicine, AHAF-supported researchers reported that brains expressing ApoE4 versus other forms of ApoE aren't as good in clearing the toxic beta-amyloid peptide. This build-up leads to increased plaque deposits, a hallmark of Alzheimer's disease.
Mice that make different forms of the APOE protein have different levels of Alzheimer's plaques, a hallmark of this devastating illness.
Photo courtesy of David Holtzman, M.D., Washington University School of Medicine in St. Louis and Science Translational Medicine
This ground-breaking discovery offers a new path for researchers to discover novel prevention and treatment approaches for Alzheimer's disease. In the future, a drug could be designed to speed up the beta-amyloid clearance and prevent the plaques from forming in the brain.
Scientists have found that a protein made by a key Alzheimer’s gene slows the brain’s ability to get rid of amyloid beta, the main ingredient of the amyloid plaques that characterize the devastating illness.
The research, in humans and mice, links slow amyloid beta clearance rates to one form of the apolipoprotein E (APOE) gene.
The finding moves researchers closer to understanding a major risk factor for Alzheimer’s disease and may point to natural pathways for clearing amyloid beta that can be enhanced pharmaceutically. Scientists at Washington University School of Medicine in St. Louis report the results this week in Science Translational Medicine.
APOE comes in three forms: E2, E3 and E4. Neurologists have been interested because of genetic studies showing that APOE E4 substantially increases Alzheimer’s risk and lowers age of onset by 10 to 15 years.
“We knew that APOE was linked with amyloid beta accumulation and suspected that APOE E4 might slow amyloid-beta clearance. This study directly shows that this is particularly true for APOE E4,” says David Holtzman, MD, the Andrew B. and Gretchen P. Jones Professor and head of the Department of Neurology at Washington University. “The next step is to find out how APOE affects amyloid beta clearance and how APOE E4 disrupts that process, with the eventual goal of developing ways to enhance clearance.”
To begin the study, scientists analyzed the APOE genes in nearly 300 healthy human volunteers and used scans and cerebrospinal fluid to determine approximately how much amyloid plaque deposition the volunteers had in their brains. Those with one or two copies of the E4 form of the APOE gene were much more likely to have plaque deposition compared to individuals with other versions of APOE. Although all of the volunteers were healthy, amyloid plaque deposition and other brain changes associated with Alzheimer’s disease begin as much as 10 to 15 years or more before clinical symptoms become apparent.
APOE’s normal roles in the brain are still somewhat unclear. In the rest of the body, it circulates in the blood and plays an important role in controlling cholesterol levels.
Some causes of Alzheimer’s disease increase the brain’s production of amyloid beta, but scientists did not know whether APOE E4 caused more amyloid beta production or slowed its removal. To answer that question, Joseph Castellano, a doctoral student in Holtzman’s laboratory, worked with mice genetically altered to develop brain changes similar to Alzheimer’s and to exclusively make one of the three human forms of APOE.
Castellano used a technique called in vivo microdialysis to monitor amyloid beta levels in the brains of mice. He found that young adult mice that made APOE E4 had significantly higher levels of amyloid beta in their brains, and they cleared amyloid beta much more slowly than mice producing APOE E2 or E3. When he assessed amyloid plaque deposition in older mice, those that produced APOE E4 had many more plaques than mice that made APOE E2 or APOE E3.
To determine whether the different forms of APOE had any effect on amyloid beta production rates, Castellano applied another technique called stable isotope labeling kinetics in collaboration with the laboratory of Randall Bateman, MD, assistant professor of neurology at Washington University. The experiment showed no significant difference in production rates in mice with each of the three forms of human APOE.
“These experiments show that APOE E4 is impairing amyloid beta clearance compared to other forms of APOE,” Castellano says. “One very significant question is whether APOE and amyloid beta interact directly or indirectly. If they do bind to each other, does this binding differ according to the form of APOE, causing the differences in clearance we observed?”
Holtzman’s laboratory has already identified a receptor in the brain that removes APOE and amyloid beta.
“We would like to find out whether that receptor clears amyloid beta and APOE together, or if the two are removed from the brain through distinct mechanisms,” Holtzman says. “Answering these questions could be very important for new therapies.”
Women at the Center of the Global Alzheimer's Epidemic
- Five-Country Survey and Women & Alzheimer's Panel -
- Highlight the Unique Impact of Alzheimer's on Women -
- Highlight the Unique Impact of Alzheimer's on Women -
PARIS, July 18, 2011 – Today the Alzheimer's Association® in conjunction with GE Healthcare held a "Women and Alzheimer's: A Global Perspective" panel discussion during the Alzheimer's Association International Conference 2011 (AAIC). The event brought together leaders in the Alzheimer's field and revealed new data from "The Value of Knowing Survey" (Survey) commissioned by Alzheimer's Europe and administered by Harvard School of Public Health. The findings explored the impact of Alzheimer's disease on women and highlighted some of the different perspectives women have about the disease compared to men in France, Germany, Spain, Poland and the United States.
36.5 million people worldwide are estimated to be living with dementia. The new data from the multi-country survey revealed:
- In all countries women were more fearful of getting Alzheimer's compared to other diseases, second only to cancer and women in France were 15 percent more afraid of developing Alzheimer's than their male counterparts.
- Likewise, women in all five countries were more concerned than men about a loved one developing Alzheimer's.
- Almost 60 percent of women in the United States and nearly 50 percent of women in France were aware that Alzheimer's is a progressive and fatal disease.
- Women in all countries, the highest being 90 percent of women in Spain, believed that government spending on Alzheimer's research should be increased, the lowest being nearly 70 percent of women in Germany.
- Women in all countries were more likely than their male counterparts to be involved in day-to-day care. In Poland there was more than a 10 percent differential.
- In addition to providing the day-to-day care, women in France and Poland were significantly more involved in the decision-making and financial support of the person living with Alzheimer's disease.
- Should men or women develop Alzheimer's, the largest percentage of respondents identified their spouse as the person who would be responsible for their primary care, with men identifying their wives 6-18 percent more often than wives identifying their husbands. In Spain there was an 18 percent difference. Also of interest was that women were more likely to rely on children or paid caregivers outside the family than men.
- Despite the fear of the disease and the fact that women are more often caregivers, women in France and the United States appear to be more optimistic that an effective treatment for Alzheimer's will be developed in the next five years, 71 and 76 percent respectively.
"With statistics consistently pointing to the fact that more women are living with Alzheimer's and caring for people with Alzheimer's, it is clear women are disproportionately affected by this disease," said Angela Geiger, Chief Strategy Officer of the Alzheimer's Association. "These insights reinforce the conclusions published in The Shriver Report: A Women's Nation Takes on Alzheimer's which found the impact of Alzheimer's on women is significant. The perspectives we see in this survey must prompt thoughtful conversations about Alzheimer's with our friends, family members and government officials to change the trajectory of Alzheimer's disease."
"The data pointing to the number of people living with Alzheimer's and the impact on those providing care is enormous, translating into overwhelming human and financial costs," Pascale Witz, president and CEO for GE Healthcare's Medical Diagnostics business. "At GE Healthcare we are driving innovation in the industry by focusing our efforts in Alzheimer's disease on earlier diagnosis, with research into new imaging compounds, new technologies and biomarkers. With early diagnosis comes earlier treatment and the potential for delays in disease progression.
Photo courtesy of David Holtzman, M.D., Washington University School of Medicine in St. Louis and Science Translational Medicine
“Gamma-secretase Activating Protein is a Therapeutic Target for Alzheimer’s Disease.”
Researchers at the Fisher Center for Alzheimer’s Disease Research laboratory, 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. “Alzheimer’s disease is a devastating disorder for which there are no satisfactory treatments. Our findings reveal that gamma-secretase activating protein is a potential target for a new class of anti-amyloid therapies,” says Dr. Greengard, a Noble Laurate.
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. “Alzheimer’s disease is a devastating disorder for which there are no satisfactory treatments. Our findings reveal that gamma-secretase activating protein is a potential target for a new class of anti-amyloid therapies,” says Dr. Greengard, a Noble Laurate.
This new breakthrough from the laboratory of Nobel Prize winner Paul Greengard, however, suggests that treatments modeled on the blockbuster cancer drug Gleevec could be the solution. 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.”
“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.”
Transplants to restore memory for Alzheimer's sufferers after brain cells grown in lab:
ALZHEIMER’S patients could soon have their memory restored with a transplant.The breakthrough comes after scientists worked out how to grow brain cells in a lab.The cells, known as neurons, work just like the originals. And yesterday the man behind the discovery revealed he was on a personal mission.Christopher Bissonnette was just a child when his beloved grand-father died of the disease.
He said: “I watched the disease slowly and relentlessly destroy his memory and individuality, and I was powerless to help him.“That experience drove me to become a scientist. I wanted to try to discover new treatments to reverse the damage.He added: “My goal was to make new healthy replacement cells that could one day be transplanted into a patient’s brain, helping their memory function again.”The neurons are relatively few in number but play a crucial role in helping to retrieve memories. In early Alzheimer’s the ability to recall is lost, not the memories themselves.
Dr Bissonnette’s team at Northwestern hospital in Chicago had to grow and test millions of cells to figure out how to turn on the exact genes to make them into the right type.Researchers have already successfully transplanted the “home-made” nerve cells into mice after perfecting a way to turn skin cells into brain cells.Calling for more funding into the pioneering project, Prof Clive Ballard, of the Alzheimer’s Society, said: “It’s very exciting. This is a major step forward.”
Scripps Research Study Points to Liver, Not Brain, as Origin of Alzheimer’s Plaques:
LA JOLLA, CA – March 3, 2011 – Unexpected results from a Scripps Research Institute and ModGene, LLC study could completely alter scientists' ideas about Alzheimer's disease—pointing to the liver instead of the brain as the source of the "amyloid" that deposits as brain plaques associated with this devastating condition. The findings could offer a relatively simple approach for Alzheimer's prevention and treatment.
The study was published online today in The Journal of Neuroscience Research.
In the study, the scientists used a mouse model for Alzheimer's disease to identify genes that influence the amount of amyloid that accumulates in the brain. They found three genes that protected mice from brain amyloid accumulation and deposition. For each gene, lower expression in the liver protected the mouse brain. One of the genes encodes presenilin—a cell membrane protein believed to contribute to the development of human Alzheimer's.
"This unexpected finding holds promise for the development of new therapies to fight Alzheimer's," said Scripps Research Professor Greg Sutcliffe, who led the study. "This could greatly simplify the challenge of developing therapies and prevention."
An estimated 5.1 million Americans have Alzheimer's disease, including nearly half of people age 85 and older. By 2050, the number of people age 65 and over with this disease will range from 11 million to 16 million unless science finds a way to prevent or effectively treat it. In addition to the human misery caused by the disease, there is the unfathomable cost. A new report from the Alzheimer's Association shows that in the absence of disease-modifying treatments, the cumulative costs of care for people with Alzheimer's from 2010 to 2050 will exceed $20 trillion.
A Genetic Search-and-Find Mission
In trying to help solve the Alzheimer's puzzle, in the past few years Sutcliffe and his collaborators have focused their research on naturally occurring, inherited differences in neurological disease susceptibility among different mouse strains, creating extensive databases cataloging gene activity in different tissues, as measured by mRNA accumulation. These data offer up maps of trait expression that can be superimposed on maps of disease modifier genes.
As is the case with nearly all scientific discovery, Sutcliffe's research builds on previous findings. Several years ago, researchers at Case Western Reserve mapped three genes that modify the accumulation of pathological beta amyloid in the brains of a transgenic mouse model of Alzheimer's disease to large chromosomal regions, each containing hundreds of genes. The Case Western scientists used crosses between the B6 and D2 strains of mice, studying more than 500 progeny.
Using the results from this study, Sutcliffe turned his databases of gene expression to the mouse model of Alzheimer's, looking for differences in gene expression that correlated with differences in disease susceptibility between the B6 and D2 strains. This intensive work involved writing computer programs that identified each genetic difference that distinguished the B6 and D2 genomes, then running mathematical correlation analysis (known as regression analysis) of each difference. Correlations were made between the genotype differences (B6 or D2) and the amount of mRNA product made from each of the more than 25,000 genes in a particular tissue in the 40 recombinant inbred mouse strains. These correlations were repeated 10 times to cover 10 tissues, the liver being one of them.
"A key aspect of this work was learning how to ask questions of massive data sets to glean information about the identities of heritable modifier genes," Sutcliffe said. "This was novel and, in a sense, groundbreaking work: we were inventing a new way to identify modifier genes, putting all of these steps together and automating the process. We realized we could learn about how a transgene's pathogenic effect was being modified without studying the transgenic mice ourselves."
Looking for a Few Good Candidates
Sutcliffe's gene hunt offered up good matches, candidates, for each of the three disease modifier genes discovered by the Case Western scientists, and one of these candidates—the mouse gene corresponding to a gene known to predispose humans carrying particular variations of it to develop early-onset Alzheimer's disease—was of special interest to his team.
"The product of that gene, called Presenilin2, is part of an enzyme complex involved in the generation of pathogenic beta amyloid," Sutcliffe explained. "Unexpectedly, heritable expression of Presenilin2 was found in the liver but not in the brain. Higher expression of Presenilin2 in the liver correlated with greater accumulation of beta amyloid in the brain and development of Alzheimer's-like pathology."
This finding suggested that significant concentrations of beta amyloid might originate in the liver, circulate in the blood, and enter the brain. If true, blocking production of beta amyloid in the liver should protect the brain.
To test this hypothesis, Sutcliffe's team set up an in vivo experiment using wild-type mice since they would most closely replicate the natural beta amyloid-producing environment. "We reasoned that if brain amyloid was being born in the liver and transported to the brain by the blood, then that should be the case in all mice," Sutcliffe said, "and one would predict in humans, too."
The mice were administered imatinib (trade name Gleevec, an FDA-approved cancer drug), a relatively new drug currently approved for treatment of chronic myelogenous leukemia and gastrointestinal tumors. The drug potently reduces the production of beta amyloid in neuroblastoma cells transfected by amyloid precursor protein (APP) and also in cell-free extracts prepared from the transfected cells. Importantly, Gleevec has poor penetration of the blood-brain barrier in both mice and humans."This characteristic of the drug is precisely why we chose to use it," Sutcliffe explained. "Because it doesn't penetrate the blood-brain barrier, we were able to focus on the production of amyloid outside of the brain and how that production might contribute to amyloid that accumulates in the brain, where it is associated with disease."The mice were injected with Gleevec twice a day for seven days; then plasma and brain tissue were collected, and the amount of beta amyloid in the blood and brain was measured. The findings: the drug dramatically reduced beta amyloid not only in the blood, but also in the brain where the drug cannot penetrate. Thus, an appreciable portion of brain amyloid must originate outside of the brain, and imatinib represents a candidate for preventing and treating Alzheimer's.
As for the future of this research, Sutcliffe says he hopes to find a partner and investors to move the work into clinical trials and new drug development.In addition to Sutcliffe, the authors of the study, titled "Peripheral reduction of β-amyloid is sufficient to reduce brain αβ: implications for Alzheimer's disease," include Peter Hedlund and Elizabeth Thomas of Scripps Research, and Floyd Bloom and Brian Hilbush of ModGene, LLC, which funded the project. For more information, see
"This unexpected finding holds promise for the development of new therapies to fight Alzheimer's," said Scripps Research Professor Greg Sutcliffe, who led the study. "This could greatly simplify the challenge of developing therapies and prevention."
An estimated 5.1 million Americans have Alzheimer's disease, including nearly half of people age 85 and older. By 2050, the number of people age 65 and over with this disease will range from 11 million to 16 million unless science finds a way to prevent or effectively treat it. In addition to the human misery caused by the disease, there is the unfathomable cost. A new report from the Alzheimer's Association shows that in the absence of disease-modifying treatments, the cumulative costs of care for people with Alzheimer's from 2010 to 2050 will exceed $20 trillion.
A Genetic Search-and-Find Mission
In trying to help solve the Alzheimer's puzzle, in the past few years Sutcliffe and his collaborators have focused their research on naturally occurring, inherited differences in neurological disease susceptibility among different mouse strains, creating extensive databases cataloging gene activity in different tissues, as measured by mRNA accumulation. These data offer up maps of trait expression that can be superimposed on maps of disease modifier genes.
As is the case with nearly all scientific discovery, Sutcliffe's research builds on previous findings. Several years ago, researchers at Case Western Reserve mapped three genes that modify the accumulation of pathological beta amyloid in the brains of a transgenic mouse model of Alzheimer's disease to large chromosomal regions, each containing hundreds of genes. The Case Western scientists used crosses between the B6 and D2 strains of mice, studying more than 500 progeny.
Using the results from this study, Sutcliffe turned his databases of gene expression to the mouse model of Alzheimer's, looking for differences in gene expression that correlated with differences in disease susceptibility between the B6 and D2 strains. This intensive work involved writing computer programs that identified each genetic difference that distinguished the B6 and D2 genomes, then running mathematical correlation analysis (known as regression analysis) of each difference. Correlations were made between the genotype differences (B6 or D2) and the amount of mRNA product made from each of the more than 25,000 genes in a particular tissue in the 40 recombinant inbred mouse strains. These correlations were repeated 10 times to cover 10 tissues, the liver being one of them.
"A key aspect of this work was learning how to ask questions of massive data sets to glean information about the identities of heritable modifier genes," Sutcliffe said. "This was novel and, in a sense, groundbreaking work: we were inventing a new way to identify modifier genes, putting all of these steps together and automating the process. We realized we could learn about how a transgene's pathogenic effect was being modified without studying the transgenic mice ourselves."
Looking for a Few Good Candidates
Sutcliffe's gene hunt offered up good matches, candidates, for each of the three disease modifier genes discovered by the Case Western scientists, and one of these candidates—the mouse gene corresponding to a gene known to predispose humans carrying particular variations of it to develop early-onset Alzheimer's disease—was of special interest to his team.
"The product of that gene, called Presenilin2, is part of an enzyme complex involved in the generation of pathogenic beta amyloid," Sutcliffe explained. "Unexpectedly, heritable expression of Presenilin2 was found in the liver but not in the brain. Higher expression of Presenilin2 in the liver correlated with greater accumulation of beta amyloid in the brain and development of Alzheimer's-like pathology."
This finding suggested that significant concentrations of beta amyloid might originate in the liver, circulate in the blood, and enter the brain. If true, blocking production of beta amyloid in the liver should protect the brain.
To test this hypothesis, Sutcliffe's team set up an in vivo experiment using wild-type mice since they would most closely replicate the natural beta amyloid-producing environment. "We reasoned that if brain amyloid was being born in the liver and transported to the brain by the blood, then that should be the case in all mice," Sutcliffe said, "and one would predict in humans, too."
The mice were administered imatinib (trade name Gleevec, an FDA-approved cancer drug), a relatively new drug currently approved for treatment of chronic myelogenous leukemia and gastrointestinal tumors. The drug potently reduces the production of beta amyloid in neuroblastoma cells transfected by amyloid precursor protein (APP) and also in cell-free extracts prepared from the transfected cells. Importantly, Gleevec has poor penetration of the blood-brain barrier in both mice and humans."This characteristic of the drug is precisely why we chose to use it," Sutcliffe explained. "Because it doesn't penetrate the blood-brain barrier, we were able to focus on the production of amyloid outside of the brain and how that production might contribute to amyloid that accumulates in the brain, where it is associated with disease."The mice were injected with Gleevec twice a day for seven days; then plasma and brain tissue were collected, and the amount of beta amyloid in the blood and brain was measured. The findings: the drug dramatically reduced beta amyloid not only in the blood, but also in the brain where the drug cannot penetrate. Thus, an appreciable portion of brain amyloid must originate outside of the brain, and imatinib represents a candidate for preventing and treating Alzheimer's.
As for the future of this research, Sutcliffe says he hopes to find a partner and investors to move the work into clinical trials and new drug development.In addition to Sutcliffe, the authors of the study, titled "Peripheral reduction of β-amyloid is sufficient to reduce brain αβ: implications for Alzheimer's disease," include Peter Hedlund and Elizabeth Thomas of Scripps Research, and Floyd Bloom and Brian Hilbush of ModGene, LLC, which funded the project. For more information, see
Chlamydophila pneumoniae cultured from the late-onset Alzheimer brain:
Int J Med Microbiol. 2008 Sep 29. [Epub ahead of print]
Initial characterization of Chlamydophila (Chlamydia) pneumoniae cultured from the late-onset Alzheimer brain.
Dreses-Werringloer U, Bhuiyan M, Zhao Y, Gérard HC, Whittum-Hudson JA, Hudson AP. Department of Immunology and Microbiology, Wayne State University School of Medicine, Gordon H. Scott Hall, 540 East Canfield Avenue, Detroit, MI 48201, USA.p
revious studies from this laboratory provided evidence that the intracellularibacterial pathogen Chlamydophila (Chlamydia pneumoniae is present in the late-onset Alzheimer's diseasei (AD) brain. Here we report culture of the organism from two AD brain samples, each of which originated from a different geographic region of North America. Culturable organisms were detectable after one and two passages in HEp-2 cells for the two samples. Both isolates, designated Tor-1 and Phi-1, were demonstrated to be authentic C. pneumoniae using PCRi assays targeting the C. pneumoniae-specific genesi Cpn0695, Cpn1046, and tyrP. Assessment of inclusion morphology and quantitation of infectious yields in epithelial (HEp-2), astrocytic (U-87 MG), and microglial (CHME-5) cell lines demonstrated an active, rather than a persistent, growth phenotype for both isolates in all host cell types. Sequencing of the omp1 gene from each isolate, and directly from DNA prepared from several additional AD brain tissue samples PCR-positive for C. pneumoniae, revealed genetically diverse chlamydial populations. Both brain isolates carry several copies of the tyrP gene, a triple copy in Tor-1, and predominantly a triple copy in Phi-1 with a minor population component having a double copy. This observation indicated that the brain isolates are more closely related to respiratory than to vascular/atheroma strains of C. pneumoniae.
Int J Med Microbiol. 2008 Sep 29. [Epub ahead of print]
Initial characterization of Chlamydophila (Chlamydia) pneumoniae cultured from the late-onset Alzheimer brain.
Dreses-Werringloer U, Bhuiyan M, Zhao Y, Gérard HC, Whittum-Hudson JA, Hudson AP. Department of Immunology and Microbiology, Wayne State University School of Medicine, Gordon H. Scott Hall, 540 East Canfield Avenue, Detroit, MI 48201, USA.p
revious studies from this laboratory provided evidence that the intracellularibacterial pathogen Chlamydophila (Chlamydia pneumoniae is present in the late-onset Alzheimer's diseasei (AD) brain. Here we report culture of the organism from two AD brain samples, each of which originated from a different geographic region of North America. Culturable organisms were detectable after one and two passages in HEp-2 cells for the two samples. Both isolates, designated Tor-1 and Phi-1, were demonstrated to be authentic C. pneumoniae using PCRi assays targeting the C. pneumoniae-specific genesi Cpn0695, Cpn1046, and tyrP. Assessment of inclusion morphology and quantitation of infectious yields in epithelial (HEp-2), astrocytic (U-87 MG), and microglial (CHME-5) cell lines demonstrated an active, rather than a persistent, growth phenotype for both isolates in all host cell types. Sequencing of the omp1 gene from each isolate, and directly from DNA prepared from several additional AD brain tissue samples PCR-positive for C. pneumoniae, revealed genetically diverse chlamydial populations. Both brain isolates carry several copies of the tyrP gene, a triple copy in Tor-1, and predominantly a triple copy in Phi-1 with a minor population component having a double copy. This observation indicated that the brain isolates are more closely related to respiratory than to vascular/atheroma strains of C. pneumoniae.
Enbrel: Anti-AD drug?
Reports of success in treating AD using injections of the arthritis drug Enbrel have sparked hope among Alzheimers patients and their families — and some concern among physicians.
A recent study reported improvement in cognitive symptoms among 15 Alzheimers patients who received weekly injections of Enbrel for six months. But doctors not involved in the research say the publicity surrounding it could lead Alzheimerspatients or their family members to believe Enbrel is a proven treatment for the disease when the study actually reflects interesting, but preliminary, research.
The pilot study was published in April by Dr. Edward Tobinick of Institute Research Associates in Los Angeles, along with three co-authors, in the peer-reviewed, electronic medical journal Medscape General Medicine.
The research explored whether Enbrel can reduce the activity of an inflammation-producing substance called tumor necrosis factor-alpha in the brains of Alzheimers patients.The 15 patients were injected in the back of the neck, above the spine. The study cited "a sustained and significant improvement in cognition" in both mild and more severe cases.
But Alzheimers experts who were not involved in the study say its too early to determine if the therapy offers real benefits because it was a small pilot study. They said a randomized, controlled trial was needed, in which some patients receive the drug and some do not, while the investigators remain unaware as to who is receiving medication.
"Its an uncontrolled study; thats important because many studies which look promising in an open study end up not being successful," says Dr. P. Murali Doraiswamy, a Duke University psychiatrist who is on the Alzheimers Foundation of Americas medical advisory board. "The study is too small for any reasonable conclusions to be drawn."
The concept behind the study — using a novel route to deliver an anti-inflammatory drug — is intriguing, says Doraiswamy. But previous research using other anti-inflammatory drugs in Alzheimers patients has failed, he says. TheAlzheimers Foundation of America does not advocate the use of anti-inflammatory drugs because of the lack of evidence that they work.
Moreover, anti-tumor necrosis factor medications, including Enbrel, have been associated with rare but serious side effects, says Dr. George Bartzokis, a neurology professor and director of the clinical core of the AD Research Center at UCLA. Enbrel is linked to infections and symptoms of multiple sclerosis.
Experts also questioned whether the drug could reach the brains of patients. Tobinick says he injected it in the neck for closer proximity to the brain.
"The delivery of this drug is fairly unusual," says Freddi Segal-Gidan, a gerontologist and co-director of the Rancho Los Amigos-USC Alzheimers Disease Research Center. "We have what is called a blood-brain barrier that is to protect the brain from agents getting in. Its unclear how much of this agent was able to get into the brain."
Tobinick, however, called the positive results "unprecedented" and says he is eager for other researchers to test the therapy.
"We would argue that this is urgently necessary due to the unmet medical needs being addressed and the degree of clinical improvement which was observed and documented," he says. "The degree of improvement and duration of improvement over six months both argue against … a placebo effect."Tobinick, a dermatologist and internist, holds patents for his Enbrel treatment methods and owns stock in Amgen Inc., which makes Enbrel. He offers Enbrel to selected Alzheimers patients outside of clinical studies.
The other three co-authors of the Alzheimers paper have no financial interest
FRIDAY, April 22 (HealthDay News) -- Regular infusions of plasma derived antibodies appear to reduce levels of Alzheimers disease-causing brain plaques while improving patients thinking ability, researchers report.
Buildup of beta-amyloid protein plaques in the brain is a hallmark of Alzheimers and toxicity related to this buildup is thought to be a major cause of the disease, for which there is currently no effective treatment.
In this phase I clinical studies, conducted by a team from New York-Presbyterian Hospital/Weill Cornell Medical Center, researchers gave patients with mild to moderate Alzheimers periodic infusions of a targeted antibody, called immunoglobulin (IVIg). The antibody makes its way to the brain where it targets beta-amyloid for removal.
The study included eight Alzheimers patients treated with IVIg. After six months of treatment, seven of the patients underwent cognitive testing. The tests showed that cognitive function stopped declining in all seven patients and had actually improved in six of the seven patients.
"If these results are confirmed in larger, controlled trials, we might have a safe AD treatment capable of clearing the amyloid protein away," senior researcher Dr. Marc E. Weksler said in a prepared statement.The study was presented at the recent annual meeting of the American Academy of Neurology in Miami.The researchers emphasize that its too soon to describe IVIg as anything more than promising, and they do not recommend that doctors treat Alzheimers patients with IVIg at this point in time. Preparations are already underway for a larger, controlled Phase II clinical trial of IVIg, the researchers said.IVIg is an antibody product derived from human plasma. The U.S. Food and Drug Administration has long approved the use of IVIg to treat other conditions, but not Alzheimers.
It has been well known that Alzheimers causes beta amyloid deposits in the brain. Antibodies against beta amyloid can be measured in C.S.F. these antibodies are reduces in patients who go on to develop Alzheimers. IVIg contains these antibodies so it is no miracle that it helps stop the disease in its track.
Coffee and Alzheimers Disease:
With the American population aging rapidly, diseases that affect the health of the elderly are becoming increasingly important. The prevalence of these conditions is increasing and is costing both insurers and taxpayers billions of dollars each year. One of the most widely-known such conditions is Alzheimers disease, which is a condition that affects the neurological health of the afflicted patient. Several studies have been done recently to determine whether there is a valid link between drinking coffee and reduction in the risk of Alzheimers disease.
In mid-2002, a hospital clinic in Portagul investigated to see if there was a link between drinking coffee and the reduction of the risk of developing Alzheimers disease. In particular, the researchers sought to determine if the caffeine in coffee could protect against the degeneration of the brain that is associated with Alzheimers disease in the period before diagnosis. They studied fifty-four patients with Alzheimers disease.
All of the patients met the Alzheimers disease and Related Disorders criteria. The researchers found that the caffeine in coffee was associated with a significantly lower risk of developing Alzheimers disease, even when other issues were taken into account.A university clinic located in Berlin, Germany, looked at the relationship between consumption of coffee and the delay in the onset of Alzheimers disease or reduction in the rate of progression of the disease. While they were unable to definitively state that the caffeine in coffee was beneficial to patients with Alzheimers disease, they did see the possibility of the link between coffee and overall neurological health.
Finally, a University in Ottawa Canada analyzed the risk factors for Alzheimers disease as part of the Canadian Study of Health and Aging. They studied more than six thousand patients aged 65 years or older between 1991 and 1996. The researchers found that consumption of coffee was associated with a reduced risk of Alzheimers disease. They concluded that the evidence from this study warranted further research and review.
While these studies have not been able to definitively state that drinking coffee reduces the risk of Alzheimers disease, there is enough evidence to warrant further research. In particular, the studies have shown that caffeine intake as when drinking coffee is at the very least related to neurological function such as the function that is lost with the onset of Alzheimers disease.
Copyright Randy Wilson, All Rights Reserved.
Boosting protein garbage disposal in brain cells protects mice from Alzheimer's disease:
Gene therapy that boosts the ability of brain cells to gobble up toxic proteins prevents development of Alzheimer's disease in mice that are predestined to develop it, report researchers at Georgetown University Medical Center. They say the treatment – which is given just once - could potentially do the same in people at the beginning stages of the disease.The study, published online in Human Molecular Genetics, demonstrates that giving brain cells extra parkin genes promotes efficient and effective removal of amyloid particles believed to be destroying the neurons from the inside. This revved up protein disposal process prevents the cells from dying and spewing amyloid proteins into the brain, where they stick together and clump into plaque, they say.
"At its core, this is a simple garbage in-garbage out therapy, and we are the first to show that this gene attacks amyloid beta inside brain cells for degradation," says the study's lead investigator, neuroscientist Charbel E-H Moussa, M.B., Ph.D.He adds that the strategy may work for other brain disorders. "Many neurodegenerative diseases are characterized by a toxic build-up of one protein or another, and this approach is designed to prevent that process early-on," he says.The novelty of Moussa's work is that he believes diseases like Alzheimer's starts when neurons are unable to get rid of toxic amyloid beta that begins to build up inside neurons – an idea that he says remains controversial, but is rapidly gaining acceptance among neuroscientists.
Moussa has documented a connection between Alzheimer's, Parkinsonism (such as Dementia with Lewy Bodies, or DLB), and Down's syndrome, finding that what these disorders have in common is a build-up of amyloid beta. In Parkinsonism, or secondary Parkinson's disease, the toxic protein may be found in Lewy bodies, which are clumps of protein that clogs the brain of people with DLB, and in some people with Parkinson's disease. People with Down's syndrome produce too much amyloid protein because they have three copies of the chromosome (21) that generates amyloid. "They have dementia because they have too much amyloid in their brains," Moussa says.
He and his colleagues developed a unique model system that mimics the early stages of these diseases. They used a lentivirus, a modified, inert form of HIV, to deliver amyloid beta into the motor cortex of rats, and showed that this produced a buildup of amyloid beta inside neurons, but not an accumulation outside of the cells. They hypothesize that once the stockpile of amyloid beta inside the cell reaches a critical level, neurons burst, and the amyloid beta proteins begin to stick together in the space between brain cells, forming plaque. Additionally, tau pathology is triggered by amyloid beta inside neurons, causing tau malfunctions, and the whole process results in increased brain inflammation.
So what Moussa and his team tested was removal of the amyloid beta buildup inside neurons. In earlier studies, they used the same model gene delivery system to express extra parkin in the brain of rats at the same time they received amyloid beta. Parkin is part of the ubiquitin ligase complex of proteins that helps target other proteins for degradation inside of the cell, and mutations in parkin are known to cause an early onset familial form of Parkinson's disease. In the earlier studies, the researchers found that in rats that had received amyloid beta, parkin effectively cleared the protein away.In this study, they used triple transgenic mice that are often used as a model of human AD. They develop intracellular amyloid beta at six months of age and extracellular amyloid beta plaque about 3-6 months later.
The researchers injected parkin in one side of the brain of young mice, and left the other side untouched, as a control to compare effects of the treatment.
They found that providing brain cells with about 50 percent more parkin protein activates two parallel garbage-removal processes within the brain. One is ubiquitination, in which errant proteins are targeted for destruction and recycling within the cell. The other process is autophagy, in which membranes form around damaged mitochondria (the cell's power plants) and these membranes fuse with lysosomes that destroys the contents. This is particularly important, Moussa says, because damaged mitochondria have been found to clog the insides of neurons affected by Alzheimer's disease, and the extra parkin seems to help clear them. That allows the cells to produce new and healthy mitochondria.
"With a normal amount of parkin, the cells are overwhelmed and cannot remove molecular debris. Extra parkin cleans everything," Moussa says.
In a second experiment, the research team found that mice given parkin genes through the lentiviral vector had 75 percent less amyloid beta plaque in their brains, compared to mice that were not treated, and that neuronal cell death was also reduced by that amount. They also showed that parkin cleared away so much amyloid beta inside cells that the function of normal glutamate neurotransmission in the hippocampus was restored. This is especially important, the authors say, because glutamate is key to memory formation, retention and retrieval. "Hypothetically, these damaged cells could restart memory formation," Moussa says.
Moussa says the research team has done all the animal work necessary for an application to begin studying the treatment in humans, starting with an analysis of safety.
He adds that if these experiments are successful, the goal will be to use the treatment as early as possible in the course of a neurodegenerative disease. "Our hope is to stop the whole process early on, but if it is later, perhaps we can halt progression," he says.
Moussa has documented a connection between Alzheimer's, Parkinsonism (such as Dementia with Lewy Bodies, or DLB), and Down's syndrome, finding that what these disorders have in common is a build-up of amyloid beta. In Parkinsonism, or secondary Parkinson's disease, the toxic protein may be found in Lewy bodies, which are clumps of protein that clogs the brain of people with DLB, and in some people with Parkinson's disease. People with Down's syndrome produce too much amyloid protein because they have three copies of the chromosome (21) that generates amyloid. "They have dementia because they have too much amyloid in their brains," Moussa says.
He and his colleagues developed a unique model system that mimics the early stages of these diseases. They used a lentivirus, a modified, inert form of HIV, to deliver amyloid beta into the motor cortex of rats, and showed that this produced a buildup of amyloid beta inside neurons, but not an accumulation outside of the cells. They hypothesize that once the stockpile of amyloid beta inside the cell reaches a critical level, neurons burst, and the amyloid beta proteins begin to stick together in the space between brain cells, forming plaque. Additionally, tau pathology is triggered by amyloid beta inside neurons, causing tau malfunctions, and the whole process results in increased brain inflammation.
So what Moussa and his team tested was removal of the amyloid beta buildup inside neurons. In earlier studies, they used the same model gene delivery system to express extra parkin in the brain of rats at the same time they received amyloid beta. Parkin is part of the ubiquitin ligase complex of proteins that helps target other proteins for degradation inside of the cell, and mutations in parkin are known to cause an early onset familial form of Parkinson's disease. In the earlier studies, the researchers found that in rats that had received amyloid beta, parkin effectively cleared the protein away.In this study, they used triple transgenic mice that are often used as a model of human AD. They develop intracellular amyloid beta at six months of age and extracellular amyloid beta plaque about 3-6 months later.
The researchers injected parkin in one side of the brain of young mice, and left the other side untouched, as a control to compare effects of the treatment.
They found that providing brain cells with about 50 percent more parkin protein activates two parallel garbage-removal processes within the brain. One is ubiquitination, in which errant proteins are targeted for destruction and recycling within the cell. The other process is autophagy, in which membranes form around damaged mitochondria (the cell's power plants) and these membranes fuse with lysosomes that destroys the contents. This is particularly important, Moussa says, because damaged mitochondria have been found to clog the insides of neurons affected by Alzheimer's disease, and the extra parkin seems to help clear them. That allows the cells to produce new and healthy mitochondria.
"With a normal amount of parkin, the cells are overwhelmed and cannot remove molecular debris. Extra parkin cleans everything," Moussa says.
In a second experiment, the research team found that mice given parkin genes through the lentiviral vector had 75 percent less amyloid beta plaque in their brains, compared to mice that were not treated, and that neuronal cell death was also reduced by that amount. They also showed that parkin cleared away so much amyloid beta inside cells that the function of normal glutamate neurotransmission in the hippocampus was restored. This is especially important, the authors say, because glutamate is key to memory formation, retention and retrieval. "Hypothetically, these damaged cells could restart memory formation," Moussa says.
Moussa says the research team has done all the animal work necessary for an application to begin studying the treatment in humans, starting with an analysis of safety.
He adds that if these experiments are successful, the goal will be to use the treatment as early as possible in the course of a neurodegenerative disease. "Our hope is to stop the whole process early on, but if it is later, perhaps we can halt progression," he says.
Provided by Georgetown University Medical Center
Tau-induced memory loss ing Alzheimer's mice is reversible:
Amyloid-beta and tau protein deposits in the brain are characteristic features of Alzheimer disease. The effect on the hippocampus, the area of the brain that plays a central role in learning and memory, is particularly severe. However, it appears that the toxic effect of tau protein is largely eliminated when the corresponding tau gene is switched off.
Researchers from the Max Planck Research Unit for Structural Molecular Biologyat DESY in Hamburg have succeeded in demonstrating that once the gene is deactivated, mice with a human tau gene, which previously presented symptoms of dementia, regain their ability to learn and remember, and that the synapses of the mice also reappear in part. The scientists are now testing active substances to prevent the formation of tau deposits in mice. This may help to reverse memory loss in the early stages of Alzheimer disease – in part, at least.
Whereas aggregated amyloid-beta protein forms insoluble clumps between the neurons, the tau protein accumulates inside them. Tau protein stabilises the tube-shaped fibers of the cytoskeleton, known as microtubules, which provide the “rails” for cellular transport. In Alzheimer disease, excess phosphate groups cause the tau protein to malfunction and form clumps (the ‘neurofibrillary tangles’). As a result, nutrient transport breaks down and the neurons and their synapses die off. This process is accompanied by the initial stage of memory loss.
Tissue tests showed that, as expected, no tau clumps had formed in the brains of the first group of mice expressing anti-aggregant tau. In the second group – the mice suffering from Alzheimer’s – co-aggregates from human tau and “mouse tau” were formed - against expectations, because tau protein from mice does not usually aggregate. “Even more astonishingly, weeks after the additional gene had been switched off, the aggregated human tau had dissolved again. However, the ‘mouse tau’ remained clumped. Despite this, the mice were able to learn and remember again,” says Eckhard Mandelkow. More precise tests revealed that new synapses had actually formed in their brains.
The scientists concluded from this that mutated or pathological tau can alter healthy tau. It appears that pro-aggregant tau can act similar to a crystal nucleus – once it has started to clump up, it drags neighboring "healthy" tau into the clumps as well. This is what makes the process so toxic to the neurons. “The really important discovery here, however, is that the progression of Alzheimer’s disease can be reversed in principle - at least at an early stage of the illness before too many neurons have been destroyed,” explains Eva Mandelkow who, together with her husband, will be awarded the Potamkin Prize 2011 for Alzheimer's disease research, which is sponsored by the American Academy of Neurology.
The aggregation of tau proteins, however, cannot simply be switched off in humans the way it can in the transgenic mice. Nevertheless, special substances exist that could dissolve the tau aggregates. By screening 200,000 substances, the Hamburg researchers have already identified several classes of active substances that could re-convert the tau aggregates into soluble tau. These are now being tested on animals.
More information: Astrid Sydow, et al. Tau-induced Defects in Synaptic Plasticity, Learning and Memory are reversible in Transgenic Mice after Switching off the Toxic Tau Mutant, Journal of Neuroscience, February 16, 2011
Whereas aggregated amyloid-beta protein forms insoluble clumps between the neurons, the tau protein accumulates inside them. Tau protein stabilises the tube-shaped fibers of the cytoskeleton, known as microtubules, which provide the “rails” for cellular transport. In Alzheimer disease, excess phosphate groups cause the tau protein to malfunction and form clumps (the ‘neurofibrillary tangles’). As a result, nutrient transport breaks down and the neurons and their synapses die off. This process is accompanied by the initial stage of memory loss.
Together with colleagues from Leuven, Hamburg and Erlangen, Eva and Eckhard Mandelkow’s team from the Max Planck Research Unit for Structural Molecular Biology generated regulatable transgenic mice with two different human tau gene variants that can be switched on and off again: one group was given a form of the protein that cannot become entangled (anti-aggregant), and a second was provided with the code for the strongly aggregating protein variant (pro-aggregant). The mice with the first form developed no Alzheimer symptoms; the rodents that were given the pro-aggregant tau developed the disease.The scientists measured the mice’s memory loss with the help of a swimming test: the healthy mice quickly learn how to find a life-saving platform located under the surface of the water in a water basin. In contrast, the transgenic animals, which have the additional pro-aggregant tau gene paddle aimlessly around the basin until they accidentally stumble on the platform; they require over four times more time to do this than their healthy counterparts. However, if the mutated toxic tau gene is switched off again, the mice learn to reach “dry land” with ease just a few weeks later. As a control, the mice with the anti-aggregant form of tau have no defects in learning, just as normal non-transgenic mice.
The scientists concluded from this that mutated or pathological tau can alter healthy tau. It appears that pro-aggregant tau can act similar to a crystal nucleus – once it has started to clump up, it drags neighboring "healthy" tau into the clumps as well. This is what makes the process so toxic to the neurons. “The really important discovery here, however, is that the progression of Alzheimer’s disease can be reversed in principle - at least at an early stage of the illness before too many neurons have been destroyed,” explains Eva Mandelkow who, together with her husband, will be awarded the Potamkin Prize 2011 for Alzheimer's disease research, which is sponsored by the American Academy of Neurology.
The aggregation of tau proteins, however, cannot simply be switched off in humans the way it can in the transgenic mice. Nevertheless, special substances exist that could dissolve the tau aggregates. By screening 200,000 substances, the Hamburg researchers have already identified several classes of active substances that could re-convert the tau aggregates into soluble tau. These are now being tested on animals.
More information: Astrid Sydow, et al. Tau-induced Defects in Synaptic Plasticity, Learning and Memory are reversible in Transgenic Mice after Switching off the Toxic Tau Mutant, Journal of Neuroscience, February 16, 2011
Provided by Max-Planck-Gesellschaft
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