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Cited by 255Neuroinflammation and Neurodegeneration MechanismsAlzheimer's disease research and treatmentsDementia and Cognitive Impairment Research

APOE mediated neuroinflammation and neurodegeneration in Alzheimer’s disease

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Parhizkar, Samira, Holtzman, David M.·2022·Seminars in Immunology
DOI 10.1016/j.smim.2022.101594PMC PMC9411266
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Abstract

Neuroinflammation is a central mechanism involved in neurodegeneration as observed in Alzheimer's disease (AD), the most prevalent form of neurodegenerative disease. Apolipoprotein E4 (APOE4), the strongest genetic risk factor for AD, directly influences disease onset and progression by interacting with the major pathological hallmarks of AD including amyloid-β plaques, neurofibrillary tau tangles, as well as neuroinflammation. Microglia and astrocytes, the two major immune cells in the brain, exist in an immune-vigilant state providing immunological defense as well as housekeeping functions that promote neuronal well-being. It is becoming increasingly evident that under disease conditions, these immune cells become progressively dysfunctional in regulating metabolic and immunoregulatory pathways, thereby promoting chronic inflammation-induced neurodegeneration. Here, we review and discuss how APOE and specifically APOE4 directly influences amyloid-β and tau pathology, and disrupts microglial as well as astroglial immunomodulating functions leading to chronic inflammation that contributes to neurodegeneration in AD.

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  • Mounting evidence shows that APOE downstream effects converge on the microglial response to protein aggregates.

    “Indeed, mounting evidence shows that APOE downstream effects converge on the microglial response to protein aggregates, as further discussed subsequently129,130.”

    From Multifaceted roles of APOE in Alzheimer disease (2024) · cites this paper as [129]

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Cited by

Sorted by citations

Authors
Parhizkar, S., & Holtzman, D. M.
Affiliations
Washington University in St. Louis (US)
Corresponding author
Holtzman, David M.
ORCID
Venue
Seminars in Immunology
Publisher
Elsevier BV
Published
2022-01
Volume
59
Pages
101594
ISSN
1044-5323 (ISSN-L)
DOI
10.1016/j.smim.2022.101594
PMC
PMC9411266
OpenAlex
W4214714809
Cited by
255
References
62
Citations by year
2026: 64 · 2025: 79 · 2024: 53 · 2023: 45 · 2022: 14
FWCI
4.87
Type
journal article
Language
en
Open access
Licence
Locations
  • Seminars in Immunology (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • Digital Commons@Becker (Washington University School of Medicine) (submittedVersion, cc-by-nc-nd)
Funders
  • National Institute on Aging (U19AG069701, 2RF1AG047644)
  • National Institute of Neurological Disorders and Stroke (RF1NS090934)
  • Cure Alzheimer's Fund
  • National Institutes of Health
  • Michigan Department of Mental Health
  • JPB Foundation
  • Alzheimer's Association (AARF-21-850865)
Topics
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
Keywords
Alzheimer's disease, APOE ε4, neuroinflammation, neurodegeneration, amyloid plaques, tau pathology, microglia, astrocytes, chronic inflammation, immunomodulation, genetic risk factors
MeSH terms
Neuroinflammatory Diseases, Alzheimer Disease, Humans, Inflammation, Neurodegenerative Diseases, Apolipoprotein E4

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