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

Nat Aging. 2021 Nov;1(11):1002-1009. doi: 10.1038/s43587-021-00117-4. Epub 2021 Oct 7.

Abstract

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.

Publication types

  • Letter
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease* / diagnostic imaging
  • Amyloid beta-Peptides / genetics
  • Apolipoprotein E4 / genetics
  • Genotype
  • Humans
  • Memory, Short-Term

Substances

  • Amyloid beta-Peptides
  • Apolipoprotein E4