Data_Sheet_1_T Cell Responses to Neural Autoantigens Are Similar in Alzheimer’s Disease Patients and Age-Matched Healthy Controls.pdf

Alzheimer’s disease (AD), a chronic multifactorial and complex neurodegenerative disorder is a leading cause of dementia. Recently, neuroinflammation has been hypothesized as a contributing factor to AD pathogenesis. The role of adaptive immune responses against neuronal antigens, which can either confer protection or induce damage in AD, has not been fully characterized. Here, we measured T cell responses to several potential antigens of neural origin including amyloid precursor protein (APP), amyloid beta (Aβ), tau, α-synuclein, and transactive response DNA binding protein (TDP-43) in patients with AD and age-matched healthy controls (HC). Antigen-specific T cell reactivity was detected for all tested antigens, and response to tau-derived epitopes was particularly strong, but no significant differences between individuals with AD and age-matched HC were identified. We also did not observe any correlation between the antigen-specific T cell responses and clinical variables including age, gender, years since diagnosis and cognitive score. Additionally, further characterization did not reveal any differences in the relative frequency of major Peripheral Blood Mononuclear Cells (PBMC) subsets, or in the expression of genes between AD patients and HC. These observations have not identified a key role of neuronal antigen-specific T cell responses in AD.

阿尔茨海默病（Alzheimer’s disease, AD）是一种慢性、多因素且复杂的神经退行性疾病，亦是痴呆的首要致病原因。近年来，神经炎症被假说为阿尔茨海默病发病机制的潜在促成因素。针对神经元抗原的适应性免疫应答（adaptive immune responses）在阿尔茨海默病中既可发挥保护作用，也可诱导损伤，但其具体作用尚未被完全阐明。本研究对阿尔茨海默病患者与年龄匹配的健康对照（healthy controls, HC）体内，针对多种神经来源潜在抗原的T细胞应答进行了检测，所涉抗原包括淀粉样前体蛋白（amyloid precursor protein, APP）、β淀粉样蛋白（amyloid beta, Aβ）、tau蛋白、α-突触核蛋白以及反式应答DNA结合蛋白（transactive response DNA binding protein, TDP-43）。所有受试抗原均能检测到抗原特异性T细胞反应，其中针对tau蛋白衍生表位的应答尤为强烈，但未发现阿尔茨海默病患者与年龄匹配健康对照之间存在显著差异。此外，本研究未观察到抗原特异性T细胞应答与临床变量（包括年龄、性别、确诊年限及认知评分）之间存在任何相关性。进一步的特征分析亦未发现，阿尔茨海默病患者与健康对照之间，主要外周血单个核细胞（Peripheral Blood Mononuclear Cells, PBMC）亚群的相对频率或基因表达存在任何差异。上述研究结果表明，神经元抗原特异性T细胞应答在阿尔茨海默病中并未发挥关键作用。