In addition, the apolipoprotein E (APOE) ε4 allele, a well-established genetic risk factor for late-onset Alzheimer's disease, has been shown to interact with vascular risk factors to accelerate neurodegeneration via mechanisms involving amyloid deposition, neuroinflammation, and vascular dysfunction.15, 16, 17 However, whether these interactions differ by sex remains under debate.18 Here, APOE is linked to early-onset autosomal dominant Alzheimer disease.