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

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

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

14 Scopus citations


Although APOE ε4 carriers are at substantially higher risk of developing Alzheimer’s disease than noncarriers1, 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 years), 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.

Original languageAmerican English
Pages (from-to)1002-1009
Number of pages8
JournalNature Aging
Issue number11
StatePublished - Nov 2021

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© 2021, The Author(s), under exclusive licence to Springer Nature America, Inc.


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