APOE and Alzheimer disease: Due to the implication of helix 4 (~130–164) in TREM2 recognition [11,12], even moderate changes in local dynamics or occasional β-structure in G165W (APOE4) and very low, brief β transients in L155W/D151F (APOE3) could alter how APOE presents this state-dependent interface, with potential consequences for microglial signaling and contributing to AD pathogenesis [7,30].