PICALM and Alzheimer disease: From a genetic point of view, the known risk loci (such as ABCA7, APOE, CLU, CR1, BIN1, CD2AP, EPHA1, MS4A6A–MS4A4E, and PICALM genes) [5], showed a low penetrance in causing AD, except for Aβ production-related genes, and none of them have been related to different AD pathogenic pathways.