4.6 Article

Superior short-term memory in APOE ε2 carriers across the age range

Journal

BEHAVIOURAL BRAIN RESEARCH
Volume 397, Issue -, Pages -

Publisher

ELSEVIER
DOI: 10.1016/j.bbr.2020.112918

Keywords

Short-term memory; Apolipoprotein, APOE e2, Alzheimer's disease

Funding

  1. Wellcome Trust [104571/Z/14/Z, 098282/Z/12/Z, 203130/Z/16/Z]
  2. British Academy
  3. National Institute for Health Research (NIHR) based at Oxford University Hospitals NHS Trust
  4. NIHR Oxford Health Biomedical Research Centre
  5. Wellcome Trust [098282/Z/12/Z] Funding Source: Wellcome Trust

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The APOE gene is associated with individual cognitive health in aging, with the ε2 allele potentially protecting against Alzheimer's disease. Individuals carrying the ε2 allele show a significant memory advantage in short-term memory tasks, regardless of difficulty level and age, suggesting a phenotypical effect on cognition independent of later-life genetic effects.
The Apolipoprotein-E (APOE) gene is now known to be associated with individual differences in cognitive health in ageing. However, while the APOE epsilon 4 allele confers significantly increased risk of developing Alzheimer's disease (AD), the APOE epsilon 2 allele is hypothesized to be protective against the development of AD. This is in line with neuroimaging and pathological findings associated with epsilon 2 APOE allele, which go in the opposite direction to those observed in AD-related pathology. However, the precise impact of this allele on cognition remains inconclusive, with some small-cohort studies raising the possibility of an advantageous memory performance in these individuals. Here, we tested short-term memory (STM) performance in a large cohort of individuals, 300 of which were epsilon 2/epsilon 3 carriers. Their performance was compared to 554 epsilon 3/epsilon 3 carriers. We included participants from a wide age range spanning young, middle-aged and elderly adults. All of them performed a STM task that has previously been shown to be sensitive to subtle changes in memory in various patient and at-risk cohorts. Individuals carrying the APOE-epsilon 2 allele exhibited a significant memory advantage, regardless of STM task difficulty and across all ages. The observed memory advantage was present across the age range, suggestive of a phenotypical effect of this allele on cognition, possibly independent of any effects of this genetic allele that occur later life in these individuals.

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