The differential effects of APOE ɛ4 on cerebral volumetric structures in different lifespan in community-dwelling populations (P12-6.002)

Abstract

<h3>Objective:</h3> In this study, we aimed to explore the age-related effect of APOE gene on brain volume. We hypothesized that APOE might have differential effects on brain volume in different age stages. <h3>Background:</h3> Apolipoprotein E (APOE) ɛ4 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. <h3>Design/Methods:</h3> Inhabitants in Shunyi District in Beijing aged 35 years and above and living independently were invited to join this study from 2013 to 2016. The baseline assessments, APOE genotyping and brain magnetic resonance imaging were performed. The detailed neuroimaging characteristics and brain volumes (global measures, cerebral lobes, subcortical nuclei and brainstem) 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. <h3>Results:</h3> 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 ɛ3/ɛ3 carriers accounted for 71.8%, ɛ2 allele 14.0%, and ɛ4 allele 14.2%. Compared with APOE ɛ3/ɛ3, a significant protective effect for APOE ɛ4 (+) on brain parenchyma fraction (β = 0.450, p = 0.048) was observed in subjects aged ≤60 years; in participants aged &gt;60 years, a negative effect for APOE ɛ4 (+) on hippocampus (β = 1.087, p = 0.021) was found. <h3>Conclusions:</h3> Our study reveals that APOE ɛ4 has differential effects on cerebral structures in different stages of lifespan, suggesting its complicated biological function and underlying antagonistic pleiotropy. <b>Disclosure:</b> Dr. Tang has nothing to disclose. Dr. Su has nothing to disclose. Ding-Ding Zhang has nothing to disclose. Yi Dai has nothing to disclose. Ming Yao has nothing to disclose. Lixin Zhou has nothing to disclose. Liying Cui has nothing to disclose. Shuyang Zhang has nothing to disclose. Yi-Cheng Zhu has nothing to disclose. Jun Ni has nothing to disclose.