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Scientists Find Gene Variant That May Foreshadow Alzheimer’s

Tuesday December 21, 2010
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Researchers have zeroed in on a gene variant that affects brain function long before the buildup of telltale amyloid plaques that eventually lead to dementia.

People known to have a high risk for Alzheimer’s disease had a particular form of the apolipoprotein E, according to research by scientists at the Washington University School of Medicine in St. Louis. The results ran in the Dec. 15 issue of The Journal of Neuroscience.

The researchers identified functional differences in the brains of APOE4-positive and APOE4-negative patients. In a study of 100 patients with an average age of 62, slightly fewer than half had the APOE4 variant. Earlier brain scans had shown that the subjects did not have amyloid deposits in the brain.

However, the subjects with the APOE4 variant had significant differences in the way various brain regions connected with one another, according to lead author Yvette I. Sheline, MD, a professor of psychiatry, radiology and neurology and director of Washington University’s Center for Depression Stress and Neuroimaging.

APOE4 is the most important genetic marker of the disease identified so far, according to Sheline. The subjects next will be followed to determine whether they develop amyloid deposits.

“I think a significant number of them eventually will be positive for amyloid,” Sheline said. “We hope that if some people begin to accumulate amyloid, we’ll be able to look back at our data and identify particular patterns of brain function that might eventually be used to predict who is developing Alzheimer’s disease.

“The current belief is that from the time excess amyloid begins to collect in the brain, it takes about 10 years for a person to develop dementia. But this new study would suggest we might be able to intervene even before amyloid plaques begin to form. That could give us an even longer time window to intervene once an effective treatment can be developed.”


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