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Newly Identified Genetic Marker Involved in Aggressive Alzheimer's Disease

Posted Sep 16 2010 6:50pm
Scientists have discovered a gene variation that appears to predict the rate at which Alzheimer's disease will progress.....
Alzheimer's Reading Room

Senior investigator Alison M Goate said: "People who carry this genetic marker tend to have higher tau levels at any given stage of the disease than individuals without it.

"Until now, most studies of genetic risks associated with Alzheimer's disease have looked at the risk of developing the disease, not the speed at which you will progress once you have it. The genetic marker we've identified deals with progression."

A gene variation that appears to predict the rate at which Alzheimer's disease will progress has been uncovered by an international team of Alzheimer's disease experts, led by Washington University School of Medicine in St. Louis. Published in the open-access journal PLoS Genetics, the findings help determine how rapidly Alzheimer's patients may develop full-blown dementia after their diagnosis.



A gene variation that appears to predict the rate at which Alzheimer's disease will progress has been uncovered by an international team of Alzheimer's disease experts, led by Washington University School of Medicine in St. Louis. Published in the open-access journal PLoS Genetics, the findings help determine how rapidly Alzheimer's patients may develop full-blown dementia after their diagnosis.

Alzheimer's disease, one of the most common neurodegenerative disorders, affects over 4.5 million people in the United States alone. Recent studies have found the presence of a particular form of the tau protein (ptau) in cerebrospinal fluid (CSF) to be an indicator of Alzheimer's disease. By looking at single DNA variations in 846 patients, the researchers were able to identify a genetic marker, linked to elevated ptau levels, that is associated with rapid progression of the disease.
"We have looked at data from three separate, international studies, and in all three, we found the same association. So we are confident that it is real and that this gene variant is associated with progression in Alzheimer's disease," said first author Carlos Cruchaga, PhD.
The genetic finding, combined with the ability to measure ptau in the CSF, may mean that drug inhibition of tau accumulation in the CSF might prevent or delay some of the devastating effects of Alzheimer's disease. This knowledge might initially be most useful in the design of clinical trials, according to the authors; if researchers know in advance that particular patients are going to progress at a rapid rate, they could potentially better evaluate the effects of drugs designed to slow the progression of Alzheimer's disease.
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FINANCIAL DISCLOSURE: This work was supported by grants from AstraZeneca, National Institutes of Health (AG16208, P01AG03991, P50AG05681, P01AG026276, AG23185,AG05136), the Barnes-Jewish Hospital Foundation, Ford Foundation, the Department of Veterans Affairs, and an anonymous foundation. CC has a fellowship from Fundacion Alfonso Martin Escudero. Data collection and sharing for Alzheimer's Disease Neuroimaging Initiative (ADNI) (Principal Investigator: Michael Weiner; National Institutes of Health grant U01 AG024904) is funded by the National Institute on Aging, the National Institute of Biomedical Imaging and Bioengineering (NIBIB), and through generous contributions from the following: Pfizer, Inc., Wyeth Research, Bristol-Myers Squibb, Eli Lilly and Company, GlaxoSmithKline, Merck & Co., Inc., AstraZeneca AB, Novartis Pharmaceuticals Corporation, Alzheimer's Association, Eisai Global Clinical Development, Elan Corporation plc, Forest Laboratories, and the Institute for the Study of Aging, with participation from the United States Food and Drug Administration. Industry partnerships are coordinated through the Foundation for the National Institutes of Health. The grantee organization is the Northern California Institute for Research and Education, and the study is coordinated by the Alzheimer's Disease Cooperative Study at the University of California, San Diego. ADNI data are disseminated by the Laboratory of Neuro Imaging at the University of California, Los Angeles. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

COMPETING INTERESTS: The work presented in this report is also the subject of a pending patent filed by Washington University in St. Louis, Missouri, United States of America, in which Drs. C. Cruchaga, A. M. Goate, D. M. Holtzman and A. Fagan [other authors of the study] are named as inventors. The patent is currently under option to AstraZeneca Pharmaceuticals, LP. Drs. Goate and Holtzman have acted as consultants for AstraZeneca Pharmaceuticals, LP, in 2008/2009.

CITATION: Cruchaga C, Kauwe JSK, Mayo K, Spiegel N, Bertelsen S, et al. (2010) SNPs Associated with Cerebrospinal Fluid Phospho-Tau Levels Influence Rate of Decline in Alzheimer's Disease. PLoS Genet 6(9): e1001101. doi:10.1371/journal.pgen.1001101

http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1001101




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Bob DeMarco is the editor of the Alzheimer's Reading Room and an Alzheimer's caregiver. Bob has written more than 1,810 articles with more than 92,100 links on the Internet. Bob resides in Delray Beach, FL.


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