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

UMMS Affiliation

Department of Medicine, Division of Infectious Diseases and Immunology

Publication Date


Document Type



Nervous System Diseases | Neurology | Neuroscience and Neurobiology


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.


Alzheimer's disease, Neuroimmunology

DOI of Published Version



Bettcher BM, Tansey MG, Dorothée G, Heneka MT. Peripheral and central immune system crosstalk in Alzheimer disease - a research prospectus. Nat Rev Neurol. 2021 Nov;17(11):689-701. doi: 10.1038/s41582-021-00549-x. Epub 2021 Sep 14. Erratum in: Nat Rev Neurol. 2021 Oct 8;: PMID: 34522039; PMCID: PMC8439173. Link to article on publisher's site

Journal/Book/Conference Title

Nature reviews. Neurology

Related Resources

Link to Article in PubMed

PubMed ID