Peripheral and central immune system crosstalk in Alzheimer disease - a research prospectus.
Peripheral and central immune system crosstalk in Alzheimer disease - a research prospectus.
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DOI：
10.1038/s41582-021-00549-x
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发表时间：
2021-11
期刊：
影响因子：
--
通讯作者：
Heneka MT
中科院分区：
文献类型：
--
作者：
Bettcher BM;Tansey MG;Dorothée G;Heneka MT
免疫系统调节失调是阿尔茨海默病(AD)的一个基本特征，大量证据表明中枢和外周免疫反应会随着时间的推移而发生病理变化。将阿尔茨海默病视为一种全身性免疫过程提出了一些重要的问题，如外周和中央隔室之间的沟通是如何发生的，以及这种串扰是否代表了治疗的靶点。我们建立了一个白皮书工作组来描述这一领域的现状，并概述了一份研究展望，以促进我们对AD中外周-中枢免疫串扰的理解。为了指导招股说明书，我们首先概述开创性的临床观察，这些观察表明外周免疫失调和外周-中枢免疫沟通在AD中的作用，随后是形成的动物数据，这些数据为这些临床发现的可能机制提供了见解。然后，我们提出了路线图，确定了克服概念和方法挑战所需的重要下一步步骤，未来跨学科研究的机会，以及将有希望的机械性研究转化为治疗干预措施的建议。越来越多的证据表明，阿尔茨海默病(AD)的中枢和外周免疫反应都是失调的。这份路线图回顾了这项研究的现状，并提供了一个新的研究展望，以促进我们对AD的外周-中枢免疫串扰的理解。阿尔茨海默病(AD)应被视为一种全身性疾病，涉及外周和中枢免疫间隔的动态过程。临床研究表明，阿尔茨海默病患者的外周和中枢免疫系统功能失调，与认知功能和临床状态有关，并可能随着时间的推移以一种非线性的方式改变；新的证据也表明，天然免疫过程和获得性免疫过程的作用因AD的病理阶段而异。动物研究已经为外周和中枢免疫沟通的可能机制提供了见解，包括涉及外周免疫细胞进入中枢神经系统的直接途径，以及涉及全身炎症驱动的小胶质细胞功能调节的间接途径。评估外周和中枢免疫机制的纵向临床研究需要与人口统计学不同队列中人类暴露组的全面评估相结合。动物模型中进一步的机制研究对于更好地了解外周免疫细胞向中枢神经系统的运输、适应性和先天免疫系统接口以及星形胶质细胞-小胶质细胞的串扰是至关重要的。需要进行转化性和跨学科研究，以协调不同物种之间免疫途径的差异，并开发针对疾病状态和严重程度量身定做的战略性免疫疗法。
Dysregulation of the immune system is a cardinal feature of Alzheimer disease (AD), and a considerable body of evidence indicates pathological alterations in central and peripheral immune responses that change over time. Considering AD as a systemic immune process raises important questions about how communication between the peripheral and central compartments occurs and whether this crosstalk represents a therapeutic target. We established a whitepaper workgroup to delineate the current status of the field and to outline a research prospectus for advancing our understanding of peripheral–central immune crosstalk in AD. To guide the prospectus, we begin with an overview of seminal clinical observations that suggest a role for peripheral immune dysregulation and peripheral–central immune communication in AD, followed by formative animal data that provide insights into possible mechanisms for these clinical findings. We then present a roadmap that defines important next steps needed to overcome conceptual and methodological challenges, opportunities for future interdisciplinary research, and suggestions for translating promising mechanistic studies into therapeutic interventions. Evidence is accumulating that both central and peripheral immune responses are dysregulated in Alzheimer disease (AD). This roadmap reviews the current status of this research and provides a new research prospectus to advance our understanding of peripheral–central immune crosstalk in AD. Alzheimer disease (AD) should be viewed as a systemic disease that involves dynamic processes in the peripheral and central immune compartments. Clinical studies suggest that the peripheral and central immune systems are dysregulated in AD, are related to cognitive function and clinical status, and may change in a non-linear manner over time; burgeoning evidence also suggests that the roles of innate and adaptive immune processes differ depending on the pathological stage of AD. Animal studies have provided insights into possible mechanisms for peripheral and central immune communication, including direct pathways that involve peripheral immune cell infiltration into the CNS, as well as indirect pathways that involve systemic inflammation-driven modulation of microglial function. Longitudinal clinical studies to evaluate peripheral and central immune mechanisms are needed in combination with comprehensive assessment of the human exposome in demographically diverse cohorts. Further mechanistic studies in animal models are critical to providing a better understanding of peripheral immune cell trafficking to the CNS, adaptive and innate immune system interfaces and astrocyte–microglia crosstalk. Translational and interdisciplinary studies are needed to reconcile differences in immune pathways across species and to develop strategic immune-based therapies that are tailored to disease state and severity.
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影响因子：
3.9
作者：
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通讯作者：
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影响因子：
6.1
作者：
Cao C;Arendash GW;Dickson A;Mamcarz MB;Lin X;Ethell DW
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适配器 ASC 具有传播炎症的细胞外活性和“prionoid”活性。
影响因子：
30.5
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--
影响因子：
11.2
作者：
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Frenkel, Dan
DOI：
10.3233/jad-170602
发表时间：
2018
期刊：
Journal of Alzheimer's disease : JAD
影响因子：
--
作者：
Bettcher BM;Johnson SC;Fitch R;Casaletto KB;Heffernan KS;Asthana S;Zetterberg H;Blennow K;Carlsson CM;Neuhaus J;Bendlin BB;Kramer JH
通讯作者：
Kramer JH