However, the effect size of APOE-ε4 genotype on age-related hippocampal atrophy over the adult life course is small (e.g. β = −0.05, p = 0.04 in n = 3749 between 43–69 years of age)89,50,90–93 and the biological mechanisms underpinning these relationships remain poorly understood. Here, APOE is linked to hippocampal atrophy.