A new gene that influences susceptibility to late-onset Alzheimers disease (LOAD) has been identified by an international research team that analyzed the genomes of more than a thousand people with and without the disorder. The researchers identified the gene, called GAB2, as one that appears to influence the risk of Alzheimers in people with a version of a gene called APOE, which is the best established genetic risk factor for LOAD.

LOAD is expected to become an overwhelming medical problem in the next few decades as the population ages, since it afflicts about 10% of people over 65 and almost half of people over 85.

The research team from 15 institutions, led by Eric Reiman and Dietrich Stephan, published their discovery in the June 7, 2007, issue of the journal Neuron, published by Cell Press. The researchers were supported by 20 of the National Institute on Aging's Alzheimer's Disease Centers.

Although the variant version of APOE, called epsilon 4, was well known to be associated with increased Alzheimers susceptibility, there were also hints that variants of other genes modified APOEs effects, said the researchers. However, detecting the infinitesimal genetic differences that would reveal Alzheimers susceptibility genes has been extremely difficult because of their subtle effects.

To identify such fellow traveler genes, the research team performed comparative analyses of the entire genomes of 1,411 people who were either Alzheimers-affected carriers of APOE epsilon 4 or unaffected controls. They searched for tiny genetic variations, called single-nucleotide polymorphisms, that would reveal other susceptibility genes in the carriers who had Alzheimers.

The researchers identified variations in the GAB2 genes that were highly associated with cases of LOAD. Further genetic analyses of LOAD cases and nonaffected people revealed that the gene was highly expressed in neurons that are vulnerable to the pathology of A
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Contact: Erin Doonan
edoonan@cell.com
617-397-2802
Cell Press
6-Jun-2007