APOE epsilon 4 in Depression-Associated Memory Impairment-Evidence from Genetic and MicroRNA Analyses

(1) Background: The aim of this study was to replicate a reported interaction between APOE epsilon 4 status and depression on memory function in two independent, nondemented samples from the general population and to examine the potential role of circulating plasma miRNAs. (2) Methods: The impact of the APOE epsilon 4 allele on verbal memory and the interaction with depression is investigated in two large general-population cohorts from the Study of Health in Pomerania (SHIP, total n = 6286). Additionally, biological insights are gained by examining the potential role of circulating plasma miRNAs as potential epigenetic regulators. Analyses are performed using linear regression models adjusted for relevant biological and environmental covariates. (3) Results: Current depression as well as carrying the APOE epsilon 4 allele were associated with impaired memory performance, with increasing effect for subjects with both risk factors. In a subcohort with available miRNA data subjects with current depressive symptoms and carrying APOE e4 revealed reduced levels of hsa-miR-107, a prominent risk marker for early Alzheimer's Disease. (4) Conclusions: Our results confirm the effect of depressive symptoms and APOE epsilon 4 status on memory performance. Additionally, miRNA analysis identified hsa-miR-107 as a possible biological link between APOE epsilon 4, depressive symptoms, and cognitive impairment.