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Review ArticleReview Article

Targeting Systemic Innate Immune Cells as a Therapeutic Avenue for Alzheimer Disease

Vincent Pons and Serge Rivest
Robert Dantzer, ASSOCIATE EDITOR
Pharmacological Reviews January 2022, 74 (1) 1-17; DOI: https://doi.org/10.1124/pharmrev.121.000400
Vincent Pons
Neuroscience Laboratory, CHU de Québec Research Center and Department of Molecular Medicine, Faculty of Medicine, Laval University, 2705 Laurier Boul., Québec City, QC G1V 4G2, Canada
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Serge Rivest
Neuroscience Laboratory, CHU de Québec Research Center and Department of Molecular Medicine, Faculty of Medicine, Laval University, 2705 Laurier Boul., Québec City, QC G1V 4G2, Canada
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Robert Dantzer
Neuroscience Laboratory, CHU de Québec Research Center and Department of Molecular Medicine, Faculty of Medicine, Laval University, 2705 Laurier Boul., Québec City, QC G1V 4G2, Canada
Roles: ASSOCIATE EDITOR
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Abstract

Alzheimer disease (AD) is the first progressive neurodegenerative disease worldwide, and the disease is characterized by an accumulation of amyloid in the brain and neurovasculature that triggers cognitive decline and neuroinflammation. The innate immune system has a preponderant role in AD. The last decade, scientists focused their efforts on therapies aiming to modulate innate immunity. The latter is of great interest, since they participate to the inflammation and phagocytose the amyloid in the brain and blood vessels. We and others have developed pharmacological approaches to stimulate these cells using various ligands. These include toll-like receptor 4, macrophage colony stimulating factor, and more recently nucleotide-binding oligomerization domain–containing 2 receptors. This review will discuss the great potential to take advantage of the innate immune system to fight naturally against amyloid β accumulation and prevent its detrimental consequence on brain functions and its vascular system.

Significance Statement The focus on amyloid β removal from the perivascular space rather than targeting CNS plaque formation and clearance represents a new direction with a great potential. Small molecules able to act at the level of peripheral immunity would constitute a novel approach for tackling aberrant central nervous system biology, one of which we believe would have the potential of generating a lot of interest.

Footnotes

    • Received May 17, 2021.
    • Accepted August 13, 2021.
  • This work was supported by the Canadian Institutes in Health Research (CIHR) [Grant 143279].

  • No author has an actual or perceived conflict of interest with the contents of this article.

  • https://doi.org/10.1124/pharmrev.121.000400.

  • Copyright © 2022 by The American Society for Pharmacology and Experimental Therapeutics
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Pharmacological Reviews: 74 (1)
Pharmacological Reviews
Vol. 74, Issue 1
1 Jan 2022
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Review ArticleReview Article

Innate Immunity and Alzheimer's Disease

Vincent Pons and Serge Rivest
Pharmacological Reviews January 1, 2022, 74 (1) 1-17; DOI: https://doi.org/10.1124/pharmrev.121.000400

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Review ArticleReview Article

Innate Immunity and Alzheimer's Disease

Vincent Pons and Serge Rivest
Pharmacological Reviews January 1, 2022, 74 (1) 1-17; DOI: https://doi.org/10.1124/pharmrev.121.000400
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  • Article
    • Abstract
    • I. Alzheimer Disease
    • II. Cerebral Amyloid Angiopathy
    • III. Innate Immune System
    • IV. Development of Monocytic Lineage
    • V. The Role of Monocytes
    • VI. Microglia Development and Role
    • VII. Modulation of the Innate Immune System in AD
    • VIII. Targeting the mCSF/CSFS1R Axis
    • IX. Triggering Patrolling Monocytes to Clear Vascular Aβ
    • X. Targeting TLR4
    • XI. Final Remarks
    • Acknowledgments
    • Footnotes
    • Abbreviations
    • References
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