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MGH study identifies potential Alzheimer's risk gene

Researchers from the MassGeneral Institute for Neurodegenerative Disorders (MIND) have identified a gene variant that may increase the risk of late-onset Alzheimer's disease. In the March 3 New England Journal of Medicine they report that specific changes in the gene for a protein called ubiquilin-1 are associated with an increased incidence of Alzheimer's in two large study samples. The discovery could lead to improved understanding of the disease mechanism and a new target for the development of preventive and treatment strategies.

"We believe this variant moderately but significantly raises the risk of Alzheimer's disease," says Lars Bertram, MD, of the Genetics and Aging Unit at MIND, lead author of the study. "We now have to pinpoint the biological defects that accompany this finding, which also needs to be independently replicated in other Alzheimer's sample groups." Bertram is an assistant professor of Neurology at Harvard Medical School (HMS).

Mutations that raise the risk of Alzheimer's have been found in four genes. Three of these involving the amyloid precursor, presenilin 1 and presenilin 2 proteins cause rare, inherited, early-onset forms of the devastating disorder. The only genetic variation associated with the more common late-onset form is ApoE4, which increases risk but does not directly cause the disease. Researchers expect that several additional genes that affect the risk of developing Alzheimer's may be found.

In 2003, the same research team published results of a full-genome screen of Alzheimer's patients and their affected siblings in a sample of 437 families compiled by the National Institute of Mental Health (NIMH). That study identified several potential chromosome "hotspots" that could be associated with increased risk, one of the strongest on chromosome 9. Since the gene for ubiquilin-1, which is known to interact with the presenilins, resides in the same area of chromosome 9, the researchers
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Contact: Sue McGreevey
smcgreevey@partners.org
617-724-2764
Massachusetts General Hospital
2-Mar-2005


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