P2RY12 and Alzheimer disease: The microglia from AD mice showed up-regulation of Apoe, Tyrobp, and Trem2 and downregulation of homeostatic genes such as P2ry12 and Cx3cr1. 59 Once microglia are exposed to Aβ containing plaques, TREM2-APOE pathway is activated to transform a subset of homeostatic microglia to DAM.60 In summary, TREM2/DAP12 pathway is required for the recruitment and phagocytic activity of microglia in AD brain.