[en] Peripheral inflammation, defined as inflammation that occurs outside the central nervous system, is an age-related phenomenon that has been identified as a risk factor for Alzheimer's disease. While the role of chronic peripheral inflammation has been well characterized in the context of dementia and other age-related conditions, less is known about the neurologic contribution of acute inflammatory insults that take place outside the central nervous system. Herein, we define acute inflammatory insults as an immune challenge in the form of pathogen exposure (e.g., viral infection) or tissue damage (e.g., surgery) that causes a large, yet time-limited, inflammatory response. We provide an overview of the clinical and translational research that has examined the connection between acute inflammatory insults and Alzheimer's disease, focusing on three categories of peripheral inflammatory insults that have received considerable attention in recent years: acute infection, critical illness, and surgery. Additionally, we review immune and neurobiological mechanisms which facilitate the neural response to acute inflammation and discuss the potential role of the blood-brain barrier and other components of the neuro-immune axis in Alzheimer's disease. After highlighting the knowledge gaps in this area of research, we propose a roadmap to address methodological challenges, suboptimal study design, and paucity of transdisciplinary research efforts that have thus far limited our understanding of how pathogen- and damage-mediated inflammatory insults may contribute to Alzheimer's disease. Finally, we discuss how therapeutic approaches designed to promote the resolution of inflammation may be used following acute inflammatory insults to preserve brain health and limit progression of neurodegenerative pathology.
Precision for document type :
Review article
Disciplines :
Immunology & infectious disease Neurology
Author, co-author :
Walker, Keenan A ; Laboratory of Behavioral Neuroscience, National Institute On Aging. Baltimore, Baltimore, MD, USA. Keenan.Walker@nih.gov
Le Page, Lydia M; Departments of Physical Therapy and Rehabilitation Science, and Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, CA, USA
Terrando, Niccolò; Department of Anesthesiology, Cell Biology and Immunology, Duke University Medical Center, Durham, NC, USA
Duggan, Michael R; Laboratory of Behavioral Neuroscience, National Institute On Aging. Baltimore, Baltimore, MD, USA
HENEKA, Michael ; University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB)
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
External co-authors :
yes
Language :
English
Title :
The role of peripheral inflammatory insults in Alzheimer's disease: a review and research roadmap.
National Institute on Aging Alzheimer's Association BrightFocus Foundation National Institutes of Health
Funding text :
Open Access funding provided by the National Institutes of Health (NIH). Drs. Walker and Duggan are funded by the National Institute on Aging Intramural Research Program. This work was supported, in part, by the National Institute on Aging Intramural Research Program. Dr. Le Page was supported by an Alzheimer’s Association Research Fellowship and a BrightFocus Foundation Postdoctoral Fellowship. Dr. Terrando was supported by NIA grant R01AG057525 and Alzheimer’s Association (AARG). Dr. Bettcher receives grant funding from the National Institute on Aging and the Department of Defense.
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