APOE and Alzheimer disease: Furthermore, astrocytic mitochondrial dysfunction, exacerbated by risk factors like the APOE4 genotype (Lin et al., 2019; Schmukler et al., 2020; Fortea et al., 2024), contributes directly to AD progression through oxidative stress, impaired fatty acid oxidation (FAO), glutamate accumulation, and energy deficits (Preman et al., 2021).