Emerging roles of innate and adaptive immunity in Alzheimer's disease.
Emerging roles of innate and adaptive immunity in Alzheimer's disease.
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DOI：
10.1016/j.immuni.2022.10.016
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发表时间：
2022-12-13
期刊：
影响因子：
32.4
通讯作者：
Holtzman, David M.
中科院分区：
文献类型：
--
作者：
Chen, Xiaoying;Holtzman, David M.
Chen和Holtzman回顾了先天免疫和适应性免疫的新兴作用，它们的改变，相互作用以及对阿尔茨海默病发展和进展的贡献。他们提出，靶向脑实质以及边界结构中失调的先天性和适应性免疫反应可以作为预防和治疗该疾病的重要疗法。阿尔茨海默病（Alzheimer's disease，AD）是最常见的神经退行性疾病，以细胞外淀粉样蛋白（amyloid-β，Aβ）沉积和细胞内过度磷酸化聚集的tau蛋白积聚为特征。先天免疫途径的几个关键调节因子是AD的遗传风险因素。虽然这些遗传风险因素以及体内数据指出了小胶质细胞的关键作用，但新出现的证据也指出了适应性免疫反应在疾病发病机制中的作用。我们回顾了先天免疫和适应性免疫的作用，它们的小生境，通信和AD的发展和进展的贡献。我们还总结了实质中的免疫细胞的细胞组成和生理功能，以及形成动态疾病相关免疫生态位的脑边界结构中的免疫细胞。我们建议，针对脑实质和边界结构中的先天性和适应性免疫反应，可以作为治疗AD症状前和症状阶段的重要治疗靶点。
Chen and Holtzman review the emerging roles of both innate and adaptive immunity, their alterations, interplay, and contributions to the development and progression of Alzheimer’s disease. They proposed that targeting both dysregulated innate and adaptive immune responses in brain parenchyma as well as border structures could serve as important therapeutics for preventing and treating the disease. Alzheimer’s disease (AD) is the most common neurodegenerative disease with characteristic extracellular amyloid-β (Aβ) deposition and intracellular accumulation of hyperphosphorylated, aggregated tau. Several key regulators of innate immune pathways are genetic risk factors in AD. While these genetic risk factors as well as in vivo data point to key roles for microglia, emerging evidence also points to a role of the adaptive immune response in disease pathogenesis. We review the role of innate and adaptive immunity, their niches, communication, and contributions to AD development and progression. We also summarize the cellular compositions and physiological functions of immune cells in the parenchyma together with those in the brain border structures that form a dynamic disease-related immune niche. We propose that targeting both innate and adaptive immune responses in brain parenchyma and border structures could serve as important therapeutic targets for treating both pre-symptomatic as well as the symptomatic stages of AD.
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DOI：
10.1084/jem.20200861
发表时间：
2020-11-02
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Barthélemy NR;Horie K;Sato C;Bateman RJ
通讯作者：
Bateman RJ
影响因子：
82.9
作者：
Blanchard JW;Bula M;Davila-Velderrain J;Akay LA;Zhu L;Frank A;Victor MB;Bonner JM;Mathys H;Lin YT;Ko T;Bennett DA;Cam HP;Kellis M;Tsai LH
通讯作者：
Tsai LH
影响因子：
64.8
作者：
Ahn, Ji Hoon;Cho, Hyunsoo;Koh, Gou Young
通讯作者：
Koh, Gou Young
DOI：
10.1126/science.abf9277
发表时间：
2021-07-23
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Brioschi S;Wang WL;Peng V;Wang M;Shchukina I;Greenberg ZJ;Bando JK;Jaeger N;Czepielewski RS;Swain A;Mogilenko DA;Beatty WL;Bayguinov P;Fitzpatrick JAJ;Schuettpelz LG;Fronick CC;Smirnov I;Kipnis J;Shapiro VS;Wu GF;Gilfillan S;Cella M;Artyomov MN;Kleinstein SH;Colonna M
通讯作者：
Colonna M
影响因子：
5.3
作者：
Chakravarty, S;Herkenham, M
通讯作者：
Herkenham, M