APOE and Alzheimer disease: It is well-established that ApoE ε4 allele remains the strongest genetic risk factor for AD and the ApoE ε2 allele the strongest genetic protective factor, and the understanding of ApoE pathogenesis has expanded beyond amyloid-β to tau neurofibrillary degeneration, microglia and astrocyte responses, and blood-brain barrier disruption [21, 22].