Alzheimer’s disease(AD)is the most common cause of dementia and presents with an insidious onset and long prodromal period.Despite billions spent on clinical trials and decades of research,there are currently no disease modifying therapies approved for AD.Two of the most well-appreciated risk factors for AD include female sex and the presence of the apolipoprotein s4 allele(APOE4;Riedel et al,2016).In this Perspective,we highlight how greater disease subtyping through consideration of sex and APOE4 has the potential to elucidate new disease mechanisms,biomarkers and therapeutic strategies in AD(Figure 1).