"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.

The consortium of more than 80 scientists was led by Denise Harold, Ph.D., and Julie Williams, Ph.D., and their colleagues at Cardiff University. They used brain and blood tissues made available and analyzed by dozens of laboratories in the United Kingdom, Ireland, German, Belgium, Greece and the United States.

Harold D, et al. Genome-wide association study identifies variants at CLU and PICALM associated with Alzheimer's disease. Nature Genetics, advance online publication. Sept. 6, 2009

Source: Washington University School of Medicine