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

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.

Automated summary

The dysregulation of central and peripheral immune responses in Alzheimer's disease has raised questions about the communication between these systems and its potential as a therapeutic target. While evidence suggests the importance of peripheral-central immune crosstalk in AD, further research is needed to understand the mechanisms and implications for therapeutic interventions. This roadmap provides a comprehensive overview of the current status of research in this area and outlines a research prospectus for future interdisciplinary studies.