Cited by 259Neuroinflammation and Neurodegeneration MechanismsAlzheimer's disease research and treatmentsDementia and Cognitive Impairment Research

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Understanding the Role of Systemic Inflammation in Alzheimer’s Disease

Walker, Keenan A., Ficek, Bronte N., Westbrook, Reyhan·2019·ACS Chemical Neuroscience

DOI 10.1021/acschemneuro.9b00333

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Abstract

Human and animal studies suggest that inflammation occurring outside the central nervous system (systemic inflammation) may play a key role in promoting neurodegeneration, Alzheimer's disease pathology, and cognitive decline in older adults. Systemic inflammation, which is marked by increased blood levels of circulating proinflammatory cytokines and chemokines, may occur as a result of events such as infection, chronic disease, and physical and psychological stress, but may also occur outside the context of these conditions as a result of subclinical processes such as cellular senescence. Proinflammatory cytokines within the body can promote a proinflammatory environment in the central nervous system by crossing the blood-brain barrier, signaling through endothelial cells or circumventricular organs, and by stimulating the vagus nerve, which signals the detection of inflammatory proteins via direct afferent connections to the brain stem. Through each of these routes, systemic inflammation is believed to induce reactive, proinflammatory microglia and astrocytic phenotypes which can promote tau hyperphosphorylation, β-amyloid oligomerization, complement activation, and the breakdown of neurotransmitters into potentially harmful bioactive metabolites. Together, these molecular changes are believed initiate or exacerbate neurodegenerative processes that can eventually lead to cognitive decline and dementia in vulnerable older adults.

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Authors: Walker, K. A., Ficek, B. N., & Westbrook, R.
Affiliations: Johns Hopkins University (US)
Corresponding author: Walker, Keenan A.
ORCID: Walker, Keenan A.
Ficek, Bronte N.
Westbrook, Reyhan
Venue: ACS Chemical Neuroscience
Publisher: American Chemical Society (ACS)
Published: 2019-06-26
Volume: 10
Issue: 8
Pages: 3340-3342
ISSN: 1948-7193 (ISSN-L)
DOI: 10.1021/acschemneuro.9b00333
OpenAlex: W2954317829
Cited by: 259
References: 5
Citations by year: 2026: 26 · 2025: 37 · 2024: 59 · 2023: 43 · 2022: 29 · 2021: 47 · 2020: 15 · 2019: 3
Type: journal article
Language: en
Open access: closed
Licence: doi.org/10.15223/policy-029 (stm-asf)
doi.org/10.15223/policy-037 (stm-asf)
doi.org/10.15223/policy-045 (stm-asf)
Locations: ACS Chemical Neuroscience (publishedVersion)
PubMed (publishedVersion)
Funders: National Institute on Aging (AG027668)
Topics: Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
Keywords: systemic inflammation, Alzheimer's disease, neuroinflammation, inflammatory cytokines, chemokines, blood-brain barrier, vagus nerve, microglial activation, astrocytes, tau hyperphosphorylation, amyloid oligomerization, complement activation, cellular senescence, cognitive decline, dementia, older adults
MeSH terms: Alzheimer Disease, Animals, Humans, Inflammation, Neuroimmunomodulation

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Understanding the Role of Systemic Inflammation in Alzheimer’s Disease

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