TREM2 and Alzheimer disease: Structural analysis determined that the helix 4 region of APOE (~130–164, mature numbering; add +18 for pre-APOE numbering) contributes to its LDLR-binding region [7,28,29] and has been implicated in TREM2 recognition [11,12], which is an important microglial interaction implicated in AD pathogenesis.