St. Louis -- Investigators at Washington University School of Medicine in St. Louis and the University of Madrid, Spain, have found a genetic variation that appears to increase the risk of developing Alzheimer's disease.
This finding provides a link between two substances previously implicated in the disease - APOE, a cholesterol-carrying protein, and beta-amyloid, a protein that forms plaques in the brain. Replicating the results of this preliminary study would raise hopes that drugs in the pipeline may be effective against the disorder, which affects about 4 million Americans.
Since 1993, scientists have known of a relationship between the APOE gene and Alzheimer's disease. But no one knew of a mechanism by which APOE might lead to the disorder. In addition, there are several forms of APOE, but only the form known as APOE e4 was closely related to the risk for Alzheimer's disease.
The new study, reported in the January 1998 issue of Nature Genetics, shows that other forms of APOE also can increase the risk of Alzheimer's disease and suggests how this might happen.
"We've discovered changes in the APOE gene that can alter your risk, and we found those changes in the regulatory part of the gene, which controls how much APOE protein our cells produce," said Alison M. Goate, Ph.D., associate professor of genetics in psychiatry and a lead author of the study.
Goate's team at Washington University collaborated with Spanish researchers, led by Fernando Valdivieso, Ph.D., professor and chair of molecular biology at the University of Madrid. The two groups studied individuals with Alzheimer's disease and compared them with individuals of the same age who did not have Alzheimer's disease.
In both the American and the Spanish subjects, the investigators found
three normal variations, or polymorphisms, in the promoter region of the APOE
gene. The promoter is a stretch of DNA that determines h
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Contact: Jim Dryden
dryden@medicine.WUSTL.edu
314-286-0110
Washington University School of Medicine
30-Dec-1997