The first step is a triggering receptor expressed on myeloid cells 2 (TREM2)- independent process, in which microglia transits toward to a stage 1 DAM, characterized by a reduced expression of homeostatic microglia checkpoint genes such as Cx3cr1 and P2ry12/P2ry12, and upregulation of B2m, and AD-associated genes such as Tyrobp and Apoe (Xu et al., 2022). Here, P2RY12 is linked to Alzheimer disease.