APOE and Alzheimer disease: APOE4 is the strongest genetic risk factor for sAD; data obtained from cerebral organoids generated from AD-hiPSCs carrying either the APOE3 or the APOE4 genotype indicate that, besides increased levels of Aβ species and p-Tau accumulation, the latter promotes an enhancement of stress granules, disrupted RNA metabolism, apoptosis and decreased synaptic integrity [154]; APOE4-containing AD-hiPSC-derived cultures also exhibit decreased NSC plasticity [221] and accelerated neuronal maturation [154].