Researchers find 2 more genetic risk factors for Alzheimer...(mosome 11. The power of the new Geno...)

"The power of the new Genome Wide Association Study methods is that with large datasets we can now identify genes that earlier techniques were unable to confirm," says co-author John C. Morris, M.D., of Washington University. "These new genes associated with Alzheimer's disease provide new clues about how the illness develops."

Morris, the Harvey A. and Dorismae Hacker Friedman Distinguished Professor of Neurology, is the director of Washington University's Alzheimer's Disease Research Center (ADRC). He says previous ADRC research suggests that in mice, the clustrin gene may be involved in the formation of amyloid deposits in the brain. Amyloid makes up the senile plaques that dot the brains of people with Alzheimer's.

"These genes are both significant, but their effect appears to be much smaller than that of the APOE gene," Goate says. "Using statistical methods, we've been able to estimate the amount of risk attributable to APOE at about 19 or 20 percent. The newly identified genes each come in under 10 percent, so it appears they have a much smaller effect."

But not an insignificant one, Goate says, noting that although it isn't yet clear how these new genes influence Alzheimer's disease risk, levels of clustrin tend to rise when brain tissue is injured or becomes inflamed, and some researchers have noted increased clustrin levels in the brain and cerebrospinal fluid of Alzheimer's patients.

The other gene, PICALM, appears to be involved in the breakdown of synapses, structures that allow neurons in the brain to communicate. Some scientists also hypothesize that the gene may be involved in the development of amyloid deposits, but Goate says much more work is required to identify exactly how PICALM elevates Alzheimer's risk.

She expects many more genes also are involved in Alzheimer's risk. In fact, this study identified 13 more gene variants worthy of further investigation.

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