Apolipoprotein ε4 Is Associated with Lower Brain Volume in Cognitively Normal Chinese but Not White Older Adults

Studying ethnically diverse groups is important for furthering our understanding of biological mechanisms of disease that may vary across human populations. The ε4 allele of apolipoprotein E (APOE ε4) is a well-established risk factor for Alzheimer’s disease (AD), and may confer anatomic and functional effects years before clinical signs of cognitive decline are observed. The allele frequency of APOE ε4 varies both across and within populations, and the size of the effect it confers for dementia risk may be affected by other factors. Our objective was to investigate the role APOE ε4 plays in moderating brain volume in cognitively normal Chinese older adults, compared to older white Americans. We hypothesized that carrying APOE ε4 would be associated with reduced brain volume and that the magnitude of this effect would be different between ethnic groups. We performed whole brain analysis of structural MRIs from Chinese living in America (n = 41) and Shanghai (n = 30) and compared them to white Americans (n = 71). We found a significant interaction effect of carrying APOE ε4 and being Chinese. The APOE ε4xChinese interaction was associated with lower volume in bilateral cuneus and left middle frontal gyrus (PuncorrecteduncorrectedFWE = 0.05). Our study suggests there is a differential effect of APOE ε4 on brain volume in Chinese versus white cognitively normal elderly adults. This represents a novel finding that, if verified in larger studies, has implications for how biological, environmental and/or lifestyle factors may modify APOE ε4 effects on the brain in diverse populations.研究种族多样化群体，有助于深化我们对跨人群存在差异的疾病生物学机制的认知。载脂蛋白E ε4等位基因（apolipoprotein E ε4，APOE ε4）是已被广泛证实的阿尔茨海默病（Alzheimer’s disease，AD）风险因子，且可在临床认知衰退症状出现前数年，对大脑结构与功能产生影响。APOE ε4的等位基因频率在不同人群及人群内部均存在差异，其对痴呆风险的影响强度可能受其他因素调控。本研究旨在探讨APOE ε4在认知正常的中国老年人群中对脑容量的调节作用，并与美国老年白人群体进行对比。我们提出如下假设：携带APOE ε4等位基因与脑容量降低存在关联，且该效应的强度在不同种族群体间存在差异。本研究对居住在美国的华裔（n = 41）及上海本地华裔（n = 30）的结构磁共振成像（structural MRI）数据进行全脑分析，并与美国白人群体（n = 71）进行对比。研究结果显示，携带APOE ε4等位基因与华裔身份之间存在显著的交互效应。APOE ε4与华裔身份的交互效应与双侧楔叶及左侧额中回的脑容量降低显著相关（P<FWE = 0.05）。本研究表明，APOE ε4对认知正常老年人群的脑容量存在种族差异性影响，华裔群体与美国白人群体的表现存在显著差异。该发现具有创新性，若在更大规模的研究中得到验证，将有助于揭示生物学、环境及/或生活方式因素如何在多样化人群中调控APOE ε4对大脑的影响。