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

Alzheimer Disease/immunology; Alzheimer Disease/physiopathology; Alzheimer Disease/therapy; Animals; Humans; Immune System/physiopathology; Research; Alzheimer Disease; Immune System; Neurology (clinical); Cellular and Molecular Neuroscience

Abstract :

[en] 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.

Disciplines :

Neurology

Author, co-author :

Bettcher, Brianne M ; Behavioral Neurology Section, Department of Neurology, University of Colorado Alzheimer's and Cognition Center, University of Colorado Anschutz Medical Campus, Aurora, CO, USA. brianne.bettcher@cuanschutz.edu

Tansey, Malú G; Department of Neuroscience, Center for Translational Research in Neurodegenerative Disease, University of Florida College of Medicine, Gainesville, FL, USA

Dorothée, Guillaume ; Sorbonne Université, INSERM, Centre de Recherche Saint-Antoine, CRSA, Team "Immune System and Neuroinflammation", Hôpital Saint-Antoine, Paris, France

HENEKA, Michael ; Department of Neurodegenerative Diseases & Geropsychiatry/Neurology, University of Bonn Medical Center, Bonn, Germany ; Department of Infectious Diseases and Immunology, University of Massachusetts Medical School, Worcester, MA, USA

External co-authors :

yes

Language :

English

Title :

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

Publication date :

November 2021

Journal title :

Nature Reviews. Neurology

ISSN :

1759-4758

eISSN :

1759-4766

Publisher :

Nature Research, England

Volume :

Issue :

Pages :

689 - 701

Peer reviewed :

Peer Reviewed verified by ORBi

Additional URL :

https://www.nature.com/articles/s41582-021-00549-x.pdf

Funding text :

This manuscript was facilitated by the Alzheimer’s Association International Society to Advance Alzheimer’s Research and Treatment (ISTAART), through the Immunity and Neuro-degeneration Professional Interest Area (PIA). The views and opinions expressed by the authors in this publication represent those of the authors and do not necessarily reflect those of the PIA membership, ISTAART or the Alzheimer’s Association. B.M.B. is a funded investigator of the NIH/NIA (R01 AG058772) and the Department of Defense CDMRP. M.G.T. is a funded investigator of the NIH/NIA (7RF1AG057247), the Parkinson’s Foundation and the Michael J. Fox Foundation for Parkinson’s Research. G.D. is a funded investigator of the Fondation Plan Alzheimer, Fondation pour la Recherche Medicale, LECMA/Fondation Vaincre Alzheimer and Alzheimer Research UK. M.T.H. is a funded investigator of the German Research Council (DFG) Cluster of Excellence and has received support from this work through an NIH grant (R01 AG059752-02).

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