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

The Apolipoprotein-E (APOE) gene is now known to be associated with individual differences in cognitive health in ageing. However, while the APOE ε4 allele confers significantly increased risk of developing Alzheimer's disease (AD), the APOE ε2 allele is hypothesized to be protective against the development of AD. This is in line with neuroimaging and pathological findings associated with ε2 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 ε2/ε3 carriers. Their performance was compared to 554 ε3/ε3 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-ε2 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.