PSEN1 and Alzheimer disease: As professional phagocytes, microglia play a critical role in clearing various types of debris, including apoptotic neurons, myelin debris, oxidized lipids, and degenerative synapses.43 The activity of microglia phagocytosis can be regulated by AD risk genes including APOE.44 Because the individual with homozygous APOECh and PSEN1 E280 exhibited limited spread of Tau pathology in the brain,21 we hypothesize that APOECh microglia can exhibit enhanced phagocytotic capacity to better clear Tau spreads.