The Differential Effects of APOEɛ4 on Cerebral Volumetric Structures in Different Lifespan in Community-Dwelling Populations

Article type: Research Article

Authors: Tang, Mingyu^{a; 1} | Su, Ning^{a; 1} | Zhang, Dingding^b | Dai, Yi^a | Yao, Ming^a | Zhou, Lixin^a | Cui, Liying^a | Zhang, Shuyang^c | Zhu, Yicheng^a | Ni, Jun^{a; *}

Affiliations: [a] Department of Neurology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China | [b] Medical Research Center, State Key laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China | [c] Department of Cardiology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China

Correspondence: [*] Correspondence to: Jun Ni, MD, Department of Neurology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No 1, Shuaifuyuan, Dongdan, Dongcheng District. Beijing, 100730, China. Fax: 0086 10 69156372; E-mail: [email protected].

Note: [1] These authors contributed equally to this work.

Abstract: 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 ɛ3/ɛ3 carriers account for 71.8%, ɛ2 (+) 14.0%, and ɛ4 (+) 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 > 60 years, a negative effect for APOE ɛ4 (+) on hippocampus (β  =  1.087, p = 0.021) was found. Conclusion: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.

Keywords: Age stratification, antagonistic pleiotropy, APOE ɛ4, brain structure, interaction

DOI: 10.3233/JAD-220834

Journal: Journal of Alzheimer's Disease, vol. 92, no. 2, pp. 691-700, 2023