The further identification of Alzheimer’s-disease-associated genetic variants of TREM2 Arg47His, Arg62His, and Asp87Asn, which decrease the binding of TREM2 to ApoE, as well as the identification of other proteins (SHIP1, CD2AP, RIN3, BIN1, PLCG2, CASS4, and PTKB2) associating with an increased risk of AD via modulating endocytosis, motility, and phagocytosis in microglia, suggest a central role of the latter in AD pathogenesis. Here, TREM2 is linked to early-onset autosomal dominant Alzheimer disease.