The Consortium on Alzheimer's Genetics (CAG) is a multicenter collaborative research project aimed at identifying genes involved in Alzheimer's Disease (AD). Over the past four years, we have collected almost 700 DNA samples from 318 families with at least one sibling-pair discordant for AD. Initial genotyping efforts focused on APOE and the putative AD locus on chromosome 10q24. The gene for insulin-degrading enzyme (IDE), which lies in this region, has been shown to degrade Aβ and the APP intracellular domain (AICD) in vitro. These results were recently confirmed in vivo in IDE knock-out mice (Farris et al, 2003). The IDE gene has also been found to be genetically associated with AD in an earlier family-based study (Bertram et al, SFN 2002). Using the first 155 families in the CAG sample, we employed the Family Based Association Test package to test for association with AD, and conditional logistic regression to estimate the magnitude of risk for AD for APOE ε4 and multiple SNPS in IDE. We observed the e...