Early β-amyloid accumulation in the brain is associated with peripheral T cell alterations
Early β-amyloid accumulation in the brain is associated with peripheral T cell alterations
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大脑中早期 β-淀粉样蛋白的积累与外周 T 细胞的改变有关
DOI：
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发表时间：
2023
期刊：
影响因子：
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通讯作者：
A. Gietl
中科院分区：
文献类型：
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作者：
C. Gericke;Tunahan Kirabali;R. Flury;Anna Mallone;Chiara Rickenbach;L. Kulic;V. Tosevski;C. Hock;R. Nitsch;V. Treyer;M. Ferretti;A. Gietl
神经退行性阿尔茨海默病（AD）的早期临床前诊断的快速和微创方法备受期待。适应性免疫细胞对脑β-淀粉样变性（AD的病理学标志之一）应答的证据提出了免疫标记物是否可用作脑中β-淀粉样蛋白积累的替代物的问题。在这里，我们部署多维质量细胞计数结合无偏机器学习技术，对来自横截面和纵向队列研究参与者的外周血单核细胞进行免疫表型分析。我们发现，血液中抗原经历的适应性免疫细胞的增加，特别是CD 45 RA再激活的T效应记忆（TEMRA）细胞，与脑β-淀粉样蛋白的早期积累和认知健康受试者血浆AD生物标志物的变化有关。我们的研究结果表明，临床前AD病理学与适应性免疫系统的系统性改变有关。这些免疫表型变化可能有助于在未来识别和开发新的诊断工具，用于早期AD评估，并更好地了解临床结果。
Fast and minimally invasive approaches for early, preclinical diagnosis of neurodegenerative Alzheimer’s disease (AD) are highly anticipated. Evidence of adaptive immune cells responding to cerebral β-amyloidosis, one of the pathological hallmarks of AD, has raised the question of whether immune markers could be used as proxies for β-amyloid accumulation in the brain. Here, we deploy multidimensional mass cytometry combined with unbiased machine learning techniques to immunophenotype peripheral blood mononuclear cells from study participants in cross-sectional and longitudinal cohorts. We show that increases in antigen-experienced adaptive immune cells in the blood, particularly CD45RA-reactivated T effector memory (TEMRA) cells, are associated with early accumulation of brain β-amyloid and with changes in plasma AD biomarkers in still cognitively healthy subjects. Our results suggest that preclinical AD pathology is linked to systemic alterations of the adaptive immune system. These immunophenotype changes may help in the future to identify and develop novel diagnostic tools for early AD assessment and to better understand clinical outcomes.
影响因子：
20.3
作者：
Brenchley, JM;Karandikar, NJ;Koup, RA
通讯作者：
Koup, RA
影响因子：
6.5
作者：
J. Hixson;D. T. Vernier
通讯作者：
J. Hixson;D. T. Vernier
影响因子：
30.8
作者：
Kunkle, Brian W.;Grenier-Boley, Benjamin;Pericak-Vance, Margaret A.
通讯作者：
Pericak-Vance, Margaret A.