With respect to APOE, isogenic hiPSCs to investigate the mechanisms by which APOE4 increases and APOE2 decreases AD risk (Lin et al., 2018; Wang et al., 2018; Brookhouser et al., 2021; Martens et al., 2021; Sienski et al., 2021) can be used in conjunction with in vitro injury models to determine the combinatorial effect of APOE isoforms and cell injury on the manifestation of AD-related phenotypes. The gene discussed is APOE; the disease is Alzheimer disease.