First, we selected three loci with genome-wide significant evidence of association with AD susceptibility as well as independent replication: PICALM (phosphatidylinositol-binding clathrin assembly protein) [13], CR1 (complement component 3b/4b receptor 1) [14], and CLU (clusterin or apolipoprotein J) [13], [14]. Here, PICALM is linked to Alzheimer disease.