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.

现在已知载脂蛋白-E (APOE) 基因与衰老过程中认知健康的个体差异有关。然而，虽然APOE ε4 等位基因显着增加了患阿尔茨海默病 (AD) 的风险，但假设APOE ε2 等位基因对 AD 的发展具有保护作用。这符合与 ε2 APOE相关的神经影像学和病理学发现等位基因，它们与 AD 相关病理学中观察到的方向相反。然而，这个等位基因对认知的确切影响仍然没有定论，一些小队列研究提出了这些人具有有利记忆表现的可能性。在这里，我们在一大群人中测试了短期记忆 (STM) 的表现，其中 300 人是ε2/ε3携带者。将它们的性能与 554 个ε3/ε3载体进行了比较。我们包括来自青年、中年和老年人的广泛年龄范围的参与者。他们所有人都执行了一项 STM 任务，该任务先前已被证明对各种患者和高危人群的记忆细微变化很敏感。携带APOE 的个人- ε2等位基因表现出显着的记忆优势，无论 STM 任务难度如何，并且跨越所有年龄段。观察到的记忆优势存在于整个年龄范围内，表明该等位基因对认知的表型影响，可能与这些人晚年发生的该遗传等位基因的任何影响无关。