We found a significant three-way interaction among sex, APOE ɛ4 status and cardiovascular disease risk on tau deposition in the entorhinal cortex (β = 0.04; 95% CI, 0.01–0.07; P = 0.008), inferior temporal cortex (β = 0.02; 95% CI, 0.0–0.05; P = 0.029) and meta-region (β = 0.02; 95% CI, 0.0–0.04; P = 0.042). This evidence concerns the gene APOE and cardiovascular disorder.