In the multivariate gene-based analyses of the three neuropathological phenotypes (NP, NFT, and CAA), five known AD genes—BIN1, PICALM, TSPOAP1, CASS4, and APOE—reached significant association with a P value at least one order of magnitude smaller than each of the univariate association P values. This evidence concerns the gene PICALM and Alzheimer disease.