APOE and early-onset autosomal dominant Alzheimer disease: Critically, the expression of a specific APOE variant, APOE4, is the single largest genetic risk factor for the development of Alzheimer's disease (Strittmatter et al. 1993; Saunders et al. 1993) and APOE4 homozygosity is now considered as a distinct form of genetic Alzheimer's disease (Fortea et al. 2024).