Cited by 300Neuroinflammation and Neurodegeneration MechanismsAlzheimer's disease research and treatmentsDementia and Cognitive Impairment Research

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Emerging roles of innate and adaptive immunity in Alzheimer’s disease

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Chen, Xiaoying, Holtzman, David M.·2022·Immunity

DOI 10.1016/j.immuni.2022.10.016PMC PMC9772134

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Abstract

Alzheimer's disease (AD) is the most common neurodegenerative disease, with characteristic extracellular amyloid-β (Aβ) deposition and intracellular accumulation of hyperphosphorylated, aggregated tau. Several key regulators of innate immune pathways are genetic risk factors for AD. While these genetic risk factors as well as in vivo data point to key roles for microglia, emerging evidence also points to a role of the adaptive immune response in disease pathogenesis. We review the roles of innate and adaptive immunity, their niches, their communication, and their contributions to AD development and progression. We also summarize the cellular compositions and physiological functions of immune cells in the parenchyma, together with those in the brain border structures that form a dynamic disease-related immune niche. We propose that both innate and adaptive immune responses in brain parenchyma and border structures could serve as important therapeutic targets for treating both the pre-symptomatic and the symptomatic stages of AD.

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Authors: Chen, X., & Holtzman, D. M.
Affiliations: Washington University in St. Louis (US)
Corresponding author: Holtzman, David M.
ORCID: Chen, Xiaoying
Holtzman, David M.
Venue: Immunity
Publisher: Elsevier BV
Published: 2022-12
Volume: 55
Issue: 12
Pages: 2236-2254
ISSN: 1074-7613 (ISSN-L)
DOI: 10.1016/j.immuni.2022.10.016
PMC: PMC9772134
OpenAlex: W4308510589
Cited by: 297
References: 202
Citations by year: 2026: 57 · 2025: 100 · 2024: 93 · 2023: 47
FWCI: 6.26
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 538 d)
doi.org/10.15223/policy-017 (stm-asf)
doi.org/10.15223/policy-037 (stm-asf)
doi.org/10.15223/policy-012 (stm-asf)
doi.org/10.15223/policy-029 (stm-asf)
doi.org/10.15223/policy-004 (stm-asf)
Locations: Immunity (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
Funders: National Institute on Aging (RF1AG047644)
National Institute of Neurological Disorders and Stroke (RF1NS090934)
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: Alzheimer's disease, innate immunity, adaptive immunity, microglia, amyloid-beta, tau hyperphosphorylation, genetic risk factors, neuroinflammation, immune niches, immune cell composition, therapeutic target
MeSH terms: Alzheimer Disease, Humans, Immunity, Innate, Amyloid beta-Peptides, Microglia, Neurodegenerative Diseases, Adaptive Immunity

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Emerging roles of innate and adaptive immunity in Alzheimer’s disease

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