APOE and Alzheimer disease: It is also noteworthy that macaques are APOE-ε4 homozygotes, which propels many aspects of neuroinflammation, Ca2+ dysregulation and AD pathology, helping to elucidate why this genotype increases risk of sporadic AD (Arnsten et al., 2021a; Arnsten et al., 2019; Datta and Arnsten, 2025).