Sex Differences in the Genetic Architecture of Alzheimer’s Disease

Purpose of Review Summarize sex-specific contributors to the genetic architecture of Alzheimer’s disease (AD). Recent Findings There are sex differences in the effects of apolipoprotein E ( APOE ), genes along the APOE pathway, and genes along the neurotrophic signaling pathway in predicting AD. Reported sex differences are largely driven by stronger associations among females. Evidence also suggests that genetic predictors of amyloidosis are largely shared across sexes, while sex-specific genetic effects emerge downstream of amyloidosis and drive the clinical manifestation of AD. Summary There is a lack of comprehensive assessments of sex differences in genome-wide analyses of AD and a need for more systematic reporting of sex-stratified genetic effects. The emerging emphasis on sex as a biological variable provides an opportunity for transdisciplinary collaborations aimed at addressing major analytical challenges that have hampered advancements in the field. Ultimately, sex-specific genetic association studies represent a logical first step towards precision medicine.