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

Lu, Kirsty; Nicholas, Jennifer MORCID logo; Pertzov, Yoni; Grogan, John; Husain, Masud; Pavisic, Ivanna M; James, Sarah-Naomi; Parker, Thomas D; Lane, Christopher A; Keshavan, Ashvini; +13 more...Keuss, Sarah E; Buchanan, Sarah M; Murray-Smith, Heidi; Cash, David M; Malone, Ian B; Sudre, Carole H; Coath, William; Wong, Andrew; Henley, Susie MD; Fox, Nick C; Richards, Marcus; Schott, Jonathan M; and Crutch, Sebastian J (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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This is an author accepted manuscript version of an article accepted for publication, and following peer review. Please be aware that minor differences may exist between this version and the final version if you wish to cite from it.
Available under Creative Commons: Attribution-NonCommercial-No Derivative Works 4.0

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