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Dissociable effects of APOE-epsilon4 and beta-amyloid pathology on visual working memory.

Abstract

Although APOE-epsilon4 carriers are at significantly higher risk of developing Alzheimer's disease than non-carriers(1), controversial evidence suggests that APOE-epsilon4 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 69-71), we assessed differential effects of APOE-epsilon4 and beta-amyloid pathology (quantified using (18)F-Florbetapir-PET) on visual working memory (object-location binding). In 398 cognitively normal participants, APOE-epsilon4 and beta-amyloid had opposing effects on object identification, predicting better and poorer recall respectively. epsilon4-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 epsilon4-carriers, showing that some benefits of this genotype are demonstrable in older age, even in the preclinical stages of Alzheimer's disease.

Authors

Lu, Kirsty,Nicholas, Jennifer M,Pertzov, Yoni,Grogan, John,Husain, Masud,Pavisic, Ivanna M,James, Sarah-Naomi,Parker, Thomas D,Lane, Christopher A,Keshavan, Ashvini,Keuss, Sarah E,Buchanan, Sarah M,Murray-Smith, Heidi,Cash, David M,Malone, Ian B,Sudre, Carole H,Coath, William,Wong, Andrew,Henley, Susie M D,Fox, Nick C,Richards, Marcus,Schott, Jonathan M,Crutch, Sebastian J
Published Date 2021 Nov