As we demonstrated a regional-dependent association between APOEε4 and Alzheimer’s disease pathophysiology,12,36 we hypothesized that an APOE-by-sex interactive effect modulates regional vulnerability to tau accumulation across the spectrum of clinical manifestations of Alzheimer’s disease, such that women with an APOEε4 genotype exhibit greater accumulation of tau in the medial temporal lobes. This evidence concerns the gene APOE and early-onset autosomal dominant Alzheimer disease.