The differential effects of APOE.4 on cerebral volumetric structures in different lifespan in community-dwelling populations

Background: Apolipoprotein E (APOE) is closely related to Alzheimer's disease and other age-related diseases. In recent years, several studies have shown an interaction of APOE by age on brain volume. However, validation in larger cohorts is required. Objective: We explored the age-related effect of APOE on brain volumes in a community-dwelling cohort. Methods: Inhabitants in Shunyi District in Beijing aged >= 35 years were invited to join this study from 2013 to 2016. The baseline assessments, APOE genotyping and brain magnetic resonance imaging were performed. Neuroimaging small vessel disease characteristics and brain volumes (global measures, cerebral lobes, hippocampus, brainstem, and subcortical nuclei) were acquired. The general linear model was used to analyze the interaction of APOE genotypes by age on brain volumes, and the age of 60 years was chosen as a cut-off value for stratification analysis. Results: A total of 1,105 subjects were enrolled in the final analysis with a mean age of 56.18 (9.30) years, and 37.7% were men. APOE epsilon 3/epsilon 3 carriers account for 71.8%, epsilon 2 (+) 14.0%, and epsilon 4 (+) 14.2%. Compared with APOE epsilon 3/epsilon 3, a significant protective effect for APOE epsilon 4 (+) on brain parenchyma fraction (beta = 0.450, p = 0.048) was observed in subjects aged= 60 years; in participants aged > 60 years, a negative effect for APOE epsilon 4 (+) on hippocampus (beta = 1.087, p = 0.021) was found. Conclusion: Our study reveals that APOE epsilon 4 has differential effects on cerebral structures in different stages of lifespan, suggesting its complicated biological function and underlying antagonistic pleiotropy.