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4-12-11

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New genetic risk factors for Alzheimer's Disease

In two massive studies involving thousands of DNA samples, scientists from around the world identified a number of new genes and confirmed several others that may be risk factors for late-onset Alzheimer's disease.

Alzheimer's disease is an irreversible, progressive brain disorder. Researchers believe that the disease may cause changes in the brain 10 to 20 years before symptoms of memory loss or forgetfulness are noticeable. Late-onset Alzheimer's disease, the most common form of the disorder, typically appears after age 60.

Until recently only one gene, APOE, had been significantly linked to the risk for developing late-onset Alzheimer's disease. In 2009 and 2010, researchers identified three additional genes as possible risk factors. Although these new genes don't predict the development of late-onset Alzheimer's disease as strongly as APOE, their identification gives researchers an idea of the biological factors that may contribute to the disease.

To identify other genetic factors that could affect the risk of late-onset Alzheimer's, NIH's National Institute on Aging (NIA) established the Alzheimer's Disease Genetics Consortium (ADGC). ADGC helped investigators at universities and research centers from across the country to combine datasets and create a powerful tool for detecting common gene variations that may have subtle, yet important, effects on Alzheimer's disease.

A similar research effort was underway involving groups of investigators from the United Kingdom, the United States, France and other European countries. Funding for both studies came from several NIH institutes and other organizations. The results were published in two papers on April 3 in the online edition of Nature Genetics.

The ADGC conducted a genome-wide association study on DNA samples collected from more than 54,000 participants. By comparing genetic variations in Alzheimer's patients to those of cognitively normal individuals, the researchers were able to discover variants that were consistently associated with the disease.

In the ADGC study, scientists identified gene variations common to Alzheimer's patients in 4 new genes: EPHA 1, MS4A, CD2AP and CD33. The study also confirmed previously identified variants.

In the United Kingdom-based study, researchers combined the ADGC samples with samples from additional participants. Their results confirmed the variations identified by the ADGC study. They were also able to add a fifth new gene, ABCA7, to the growing list of risk factors linked to Alzheimer's.

The genes identified by these studies suggest that pathways involved in inflammation, the movement of proteins within cells and lipid transport may have a role in the disease process. These new insights will affect how scientists study Alzheimer's and develop new strategies to prevent and treat the disease.

"This is the culmination of years of work on Alzheimer's disease by a large number of scientists, yet it is just the beginning in defining how genes influence memory and intellectual function as we age. We're all tremendously excited by our progress so far, but much remains to be done, both in understanding the genetics and in defining how these genes influence the disease process," said ADGC's director, Dr. Gerard Schellenberg of the University of Pennsylvania School of Medicine.

--From the National Institute of Health

For further information on this and other health topics, visit the web site of the National Institute of Health at www.nih.gov.

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