Dissociable effects of APOE epsilon 4 and beta-amyloid pathology on visual working memory

Although APOE epsilon 4 carriers are at substantially higher risk of developing Alzheimer's disease than noncarriers(1), controversial evidence suggests that APOE epsilon 4 might confer some advantages, explaining the survival of this gene (antagonistic pleiotropy)(2,3). In a population-based cohort born in one week in 1946 (assessed aged 69-71years), we assessed differential effects of APOE epsilon 4 and beta-amyloid pathology (quantified using F-18-Florbetapir-PET) on visual working memory (object-location binding). In 398 cognitively normal participants, APOE epsilon 4 and beta-amyloid had opposing effects on object identification, predicting better and poorer recall, respectively. epsilon 4 carriers also recalled locations more precisely, with a greater advantage at higher beta-amyloid burden. These results provide evidence of superior visual working memory in epsilon 4 carriers, showing that some benefits of this genotype are demonstrable in older age, even in the preclinical stages of Alzheimer's disease.