冠状病毒和疱疹病毒抗体的蛋白质组学特征确定IGDCC4为神经退行性变的介质。
Proteomic signatures of corona and herpes viral antibodies identify IGDCC4 as a mediator of neurodegeneration.
作者信息
Duggan Michael R, Yang Shuojia, Gomez Gabriela T, Cui Yuhan, Capuano Ana W, Chen Jingsha, Yang Zhijian, Wen Junhao, Erus Guray, Drouin Shannon M, Zweibaum David, Tian Qu, Candia Julián, Bilgel Murat, Lewis Alexandria, Moghekar Abhay, Ashton Nicholas J, Kac Przemysław R, Karikari Thomas K, Blennow Kaj, Zetterberg Henrik, Maher Brion S, Spira Adam P, Dumitrescu Logan, Hohman Timothy J, Gottesman Rebecca F, Davatzikos Christos, Bennett David A, Coresh Josef, Ferrucci Luigi, Resnick Susan M, Yolken Robert, Walker Keenan A
机构信息
Laboratory of Behavioral Neuroscience, National Institute on Aging, National Institutes of Health, Baltimore, MD, USA.
Stanley Laboratory of Neurovirology, Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
出版信息
Sci Adv. 2025 May 30;11(22):eadt7176. doi: 10.1126/sciadv.adt7176.
Mechanisms underlying the dynamic relationships of viral infections and neurodegeneration warrant examination. Using a community-based cohort of older adults, the current study characterized the neurocognitive (cognitive functioning, brain volumes, Alzheimer's disease positron emission tomography, and plasma biomarkers) and plasma proteomic (7268 proteins) profiles of four common coronavirus and six herpesvirus antibody titers. Genetic inference techniques demonstrated the associations between viral antibody titers and neurocognitive outcomes may be attributed to altered expression in a subset of mechanistically relevant proteins in plasma. One of these proteins, IGDCC4 (immunoglobulin superfamily deleted in colorectal cancer subclass member 4), was related to 20-year dementia risk, cognitive functioning, and amyloid-β positivity using data from two independent cohorts, while its plasma and intrathecal abundance were causally implicated in dementia risk and clinically relevant brain atrophy. Our findings illuminate the biological basis by which host immune responses to viruses may affect neurocognitive outcomes in older adults and identify IGDCC4 as an important molecular mediator of neurodegeneration.
病毒感染与神经退行性变之间动态关系的潜在机制值得研究。本研究利用一个以社区为基础的老年人群队列，对四种常见冠状病毒和六种疱疹病毒抗体滴度的神经认知（认知功能、脑容量、阿尔茨海默病正电子发射断层扫描和血浆生物标志物）和血浆蛋白质组学（7268种蛋白质）特征进行了描述。遗传推断技术表明，病毒抗体滴度与神经认知结果之间的关联可能归因于血浆中一部分具有机制相关性的蛋白质表达的改变。其中一种蛋白质，IGDCC4（免疫球蛋白超家族在结直肠癌亚类成员4中缺失），利用来自两个独立队列的数据，与20年痴呆风险、认知功能和淀粉样β蛋白阳性相关，而其血浆和鞘内丰度与痴呆风险和临床相关脑萎缩存在因果关系。我们的研究结果阐明了宿主对病毒的免疫反应可能影响老年人神经认知结果的生物学基础，并确定IGDCC4是神经退行性变的重要分子介质。
Zotero 插件