APOE and Alzheimer disease: Second, most previous studies did not investigate an effect modification by apolipoprotein E (APOE) genotype.11,12,17,18,19,21,29 In AD mouse models, chronic sleep deprivation increased Aβ plaques, but only when they expressed human APOE4, not APOE3. 30 Previous studies in humans may have underestimated the aversive effect of disturbed sleep and 24-hour activity rhythms in APOE4 risk carriers.11,12,17,18,19,21