Dissociable effects of APOE-ε4 and β-amyloid pathology on visual working memory.

Kirsty Lu; Jennifer M Nicholas ORCID logo; Yoni Pertzov; John Grogan; Masud Husain; Ivanna M Pavisic; Sarah-Naomi James; Thomas D Parker; Christopher A Lane; Ashvini Keshavan; +13 more... Sarah E Keuss; Sarah M Buchanan; Heidi Murray-Smith; David M Cash; Ian B Malone; Carole H Sudre; William Coath; Andrew Wong; Susie MD Henley; Nick C Fox; Marcus Richards; Jonathan M Schott; Sebastian J Crutch; (2021) Dissociable effects of APOE-ε4 and β-amyloid pathology on visual working memory. Nature Aging, 1 (11). pp. 1002-1009. ISSN 2662-8465 DOI: 10.1038/s43587-021-00117-4
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Although APOE-ε4 carriers are at significantly higher risk of developing Alzheimer's disease than non-carriers1, controversial evidence suggests that APOE-ε4 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-ε4 and β-amyloid pathology (quantified using 18F-Florbetapir-PET) on visual working memory (object-location binding). In 398 cognitively normal participants, APOE-ε4 and β-amyloid had opposing effects on object identification, predicting better and poorer recall respectively. ε4-carriers also recalled locations more precisely, with a greater advantage at higher β-amyloid burden. These results provide evidence of superior visual working memory in ε4-carriers, showing that some benefits of this genotype are demonstrable in older age, even in the preclinical stages of Alzheimer's disease.


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