Trio of Gene Variants Discovered That May Raise Alzheimer's Risk

Study suggests they're implicated in clearance of amyloid plaque from brain

By Peter West
HealthDay Reporter

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SUNDAY, Sept. 6 (HealthDay News) -- Two international teams of scientists have uncovered three gene variants that up the risk for Alzheimer's disease, the most common form of dementia among the elderly and the seventh-leading cause of death in the United States.

Teams led by Dr. Philippe Amouyel of the Institut Pasteur de Lille in France, and Julie Williams, a professor of psychological medicine at Cardiff University School of Medicine in Wales, zeroed in on defects in the CLU, CR1 and PICALM genes, and also found another 13 gene variants that are solid candidates for further investigation, according to findings that appear in the Sept. 6 online issue of Nature Genetics. Until now, only four gene variants had previously been definitively associated with Alzheimer's -- APP, PS1, PS2 and APOE.

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"Although the role of these two new genes [CLU and CR1] . . . is not yet known in detail, previous studies suggest that they may be involved in the elimination of the major component of amyloid plaques," explained Amouyel, the leader of the team that studied the CLU and CR1 genes. "Genetic variants at CLU, CR1 and APOE may influence susceptibility to late-onset forms of the disease."

According to Amouyel, one group of researchers carried out a two-stage analysis of genetic samples from more than 20,000 subjects. In parallel, Williams ran a similar study, discovering the PICALM gene mutations and independently discovering the CLU gene variants.

Most of the DNA samples came from France and other European countries, but U.S. labs contributed to Williams' study as well, including the National Institute on Aging (NIA) Laboratory of Neurogenetics, the Mayo Clinic and the Washington University School of Medicine in St. Louis.

"This is the most important finding in the genetic [component] of Alzheimer's in more than 10 years," said study co-author Alison Goate, a professor of genetics in psychiatry at Washington University School of Medicine and a member of the Alzheimer's Association Medical & Scientific Advisory Council.

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