Dysregulation of the immune system is a cardinal feature of Alzheimer disease (AD), and a considerable body of evidence indicates that 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.

免疫系统失调是阿尔茨海默病 (AD) 的一个主要特征，大量证据表明中枢和外周免疫反应的病理改变会随时间而改变。将 AD 视为全身免疫过程会引发一些重要问题，即外周和中央隔室之间的通讯是如何发生的，以及这种串扰是否代表治疗目标。我们建立了一个白皮书工作组来描述该领域的现状并概述研究计划，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，我们首先概述了开创性的临床观察结果，这些观察结果表明外周免疫失调和外周-中枢免疫通讯在 AD 中的作用，随后是形成性动物数据，这些数据提供了对这些临床发现的可能机制的见解。然后，我们提出了一个路线图，其中定义了克服概念和方法挑战所需的重要后续步骤、未来跨学科研究的机会，以及将有希望的机制研究转化为治疗干预的建议。