Based on the estrogen hypothesis, we hypothesized that cognitively unimpaired older adult women would exhibit greater amyloid-β burden, reduced volume, and reduced cerebral blood flow in preclinical AD-specific brain regions (e.g., amygdala, hypothalamus, and parahippocampal gyrus) compared to men and that genetic (APOE genotype) and health risk factors (cardiometabolic disease) would predict these differences. The gene discussed is APOE; the disease is Alzheimer disease.