The relationship between the APOE genotypes and memory performance of young adults and its neural basis.

A large body of evidence consistently indicates a relationship between the apolipoprotein E (APOE) ε4 allele and memory decline in later life; however, the influence of the APOE ε4 allele on memory performance during the early stages of life remains poorly understood. Therefore, we explored whether the APOE ε4 allele is associated with cognitive advantages or disadvantages early in life from the perspective of memory function, specifically working memory and short-term memory. Based on a study of 516 university students aged 17-26 who completed short-term memory tasks and 156 students in the same age range who completed working memory tasks, our findings reveal that individuals carrying the APOE ε4 allele exhibited poorer performance in working memory, with no significant impact on short-term memory. Subsequently, employing a connectome-based predictive modeling approach in resting-state functional magnetic resonance imaging data, we defined a functional network model-dominated by default-sensorimotor network interactions that was capable of forecasting fluctuations in working memory among the held-out individuals (i.e., cross-brain prediction). Furthermore, the functional connectivity serves as a mediator in the association between APOE genotypes and working memory performance. Collectively, these findings provide novel insights into the early-life relationship between the APOE ε4 allele and memory performance, as well as its neural underpinnings.