Vacher Michael, Lee Silvia, Price Patricia, Ha Phuongnhi, Waters Shelley, Laws Simon M
CSIRO Health and Biosecurity, Australian E-Health Research Centre, Floreat, Australia.
Centre for Precision Health, Edith Cowan University, Joondalup, Australia.
BMC Neurol. 2025 Jul 1;25(1):270. doi: 10.1186/s12883-025-04279-1.
Human cytomegalovirus (CMV) is endemic worldwide. It is often acquired in childhood and persists throughout adult life. CMV is linked with several diseases of aging, but associations with cognitive performance are not consistent. Here we address whether this may reflect a dependence on putative genetic determinants, Apolipoprotein E (APOE) ε4 and Tumour Necrosis Factor (TNF), and/or the age of the subjects tested. CMV-reactive antibodies were quantitated in 419 individuals aged 71.7 [53.2-89.1] years, drawn from the Australian Imaging, Biomarker & Lifestyle (AIBL) study. Cognitive composite scores, covering five domains, a global score of cognitive performance, brain amyloid-β (Aβ) burden and demographic data were available. APOE and TNF-308 (rs1800629) genotypes were extracted from genome-wide array data. Bivariate and multivariate analyses were applied. CMV antibody levels were negatively correlated with Aβ burden and correlated directly with cognition in participants carrying the minor allele of TNF-308, notably in those lacking the APOE ε4 allele. Cognitive performance exhibited a decrease with age, but CMV antibody levels were maintained. Regression analyses revealed significant interactions between TNF-308 genotype and CMV antibody levels in the overall cohort and in participants younger than 71.1 years (median split). No such interaction was observed in those older than 71.1 years. Overall, CMV antibodies may play a protective role in carriers of the minor allele of TNF-308. This was significant in younger individuals and could be eclipsed by advanced age or carriage of the APOE ε4. The interactions described may explain disagreements in the literature regarding the effects of CMV and TNF-308.
人巨细胞病毒（CMV）在全球范围内流行。它常在儿童期感染，并在成年期持续存在。CMV与多种衰老相关疾病有关，但与认知表现的关联并不一致。在此，我们探讨这是否可能反映了对假定的遗传决定因素、载脂蛋白E（APOE）ε4和肿瘤坏死因子（TNF）以及/或者受试对象年龄的依赖性。从澳大利亚影像、生物标志物与生活方式（AIBL）研究中选取了419名年龄在71.7[53.2 - 89.1]岁的个体，对其CMV反应性抗体进行定量分析。可获取涵盖五个领域的认知综合评分、认知表现的总体评分、脑淀粉样β蛋白（Aβ）负荷以及人口统计学数据。从全基因组阵列数据中提取APOE和TNF - 308（rs1800629）基因型。应用双变量和多变量分析。CMV抗体水平与Aβ负荷呈负相关，并且与携带TNF - 308次要等位基因的参与者的认知呈正相关，尤其是在那些缺乏APOE ε4等位基因的参与者中。认知表现随年龄增长而下降，但CMV抗体水平保持稳定。回归分析显示，在整个队列以及年龄小于71.1岁（中位数分割）的参与者中，TNF - 308基因型与CMV抗体水平之间存在显著相互作用。在年龄大于71.1岁的参与者中未观察到这种相互作用。总体而言，CMV抗体可能在TNF - 308次要等位基因携带者中发挥保护作用。这在较年轻个体中显著，并且可能会因高龄或携带APOE ε4而减弱。所描述的相互作用可能解释了文献中关于CMV和TNF - 308影响的分歧。
