While mitochondrial dysfunction is acknowledged as an important factor in Alzheimer’s disease, mitochondria are typically placed downstream of Aβ and APOE, with Aβ or the APOE4 allele perturbing mitochondrial function (Area-Gomez et al., 2020; Chen et al., 2011; Mahley, 2023; Orr et al., 2019; Tambini et al., 2016; Yin et al., 2020). The gene discussed is APOE; the disease is early-onset autosomal dominant Alzheimer disease.