Peripheral and central immune system crosstalk in Alzheimer disease - a research prospectus

Autor: Guillaume Dorothée, Michael T. Heneka, Malú G. Tansey, Brianne M. Bettcher
Rok vydání: 2021
Předmět:
Zdroj: Nature Reviews. Neurology
ISSN: 1759-4766
Popis: 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.
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.
Key points 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.
Databáze: OpenAIRE
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