Alzheimer's disease genetic burden is associated with mid-life depression among persons with normal cognition.

INTRODUCTION: Despite an established link between depression and higher Alzheimer's disease (AD) risk, it is unclear whether the conditions share pathophysiology. Here, we investigated whether depression manifesting after age 50 is associated with a genetic predisposition to AD.

METHODS: From the population-based Health and Retirement Study cohort with biennial assessments of depressive symptoms and cognitive performance, we studied 6656 individuals of European ancestry with whole-genome genotyping. Polygenic risk scores (PRSs) for AD were estimated and examined for an association with depression in cognitively normal participants using regression modeling.

RESULTS: Among cognitively normal participants, those with a higher AD PRS were more likely to experience depression after age 50 after accounting for the effects of genetic predisposition to depression, sex, age, and education.

DISCUSSION: Genetic predisposition to AD may be one of the factors contributing to the pathogenesis of mid-life depression. Whether there is a shared genetic basis between mid-life depression and AD merits further study.