Investigators at Washington University in St. Louis led an international research team that has identified a new genetic risk factor for Alzheimers disease. The researchers still are working to isolate the specific gene, but they have isolated the region of DNA that contains it.

In this weeks Science, the researchers report that a region on chromosome 10 likely contains a gene that increases susceptibility to late onset Alzheimers disease. About 4 million Americans have Alzheimers, the most common form of dementia in the elderly and the fourth leading cause of death in the United States. The vast majority have the late onset form, which occurs after age 65.

One other gene is known to increase the risk of late onset Alzheimers disease. People with the E4 version of APOE (apolipoproteinE) are three to eight times more likely to develop the disease than those with other versions of the gene. But only about half of Alzheimers patients have APOE4, so other genetic and environmental factors must be important also.

"Two things about this new risk factor seem very significant," said senior investigator Alison M. Goate, Ph.D., professor of psychiatry and genetics at Washington University School of Medicine in St. Louis. "First, it appears to have as big an effect on risk as APOE4 in our sample. Secondly, it has that effect independent of APOE. It doesnt interact with that gene at all."

APOE protein is found in the lipid-protein complexes that move fats around the body. Research in mice has shown that it also interacts with a protein fragment called amyliod-beta42 (A42) to make fibrils. Such fibrils are found in the plaques that dot the brains of Alzheimers patients.

The newly-identified region on chromosome 10 also might affect A42. In an accompanying paper in the Dec. 22 issue of Science, a research team led by Stephen Younkin, M.D., Ph.D., professor of pharmacology at Mayo Clinic in Jacksonville, Fla., reports a potential mechanism. The
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Contact: Jim Dryden
dryden@medicine.wustl.edu
314-286-0110
Washington University School of Medicine
20-Dec-2000