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Cited by 147Neuroinflammation and Neurodegeneration MechanismsAlzheimer's disease research and treatmentsInflammasome and immune disorders

Microglial inflammation and phagocytosis in Alzheimer's disease: Potential therapeutic targets

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Nizami, Sohaib, Hall‐Roberts, Hazel, Warrier, Sharat, Cowley, Sally A., Di Daniel, Elena·2019·British Journal of Pharmacology
DOI 10.1111/bph.14618PMC PMC6715590
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Abstract

One of the largest unmet medical needs is a disease‐modifying treatment for Alzheimer's disease (AD). Recently, the role of microglia in disease, particularly AD, has gained great interest, following the identification of several disease risk‐associated genes that are highly expressed in microglia. Microglia play a critical homeostatic role in the brain, with neuroinflammatory and phagocytic mechanisms being of particular importance. Here, we review the role of NLRP3, the complement system, and the triggering receptor expressed in myeloid cells 2 (TREM2) in modulating microglial functions. We have reviewed the targets, their molecular pathways and the therapeutic interventions aimed at modulating these targets, in the hope of discovering a novel therapeutic approach for the treatment of AD. Linked Articles: This article is part of a themed section on Therapeutics for Dementia and Alzheimer's Disease: New Directions for Precision Medicine. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v176.18/issuetoc

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  • Microglia from individuals carrying the TREM2 R47H mutation failed to surround Aβ plaques, which correlated with an increase in filamentous amyloid deposits and phospho-tau-positive neurites in the brain.

    “microglia from individuals carrying the TREM2 R47H mutation failed to surround Aβ plaques, which correlated with an increase in filamentous amyloid deposits and phospho-tau-positive neurites in the brain [16, 103]”

    From TREM2/PLCγ2 signalling in immune cells: function, structural insight, and potential therapeutic modulation (2021) · cites this paper as [103]

    The TREM2 section reports that, in human AD brains carrying R47H or R62H, fewer microglia associate with amyloid plaques than in noncarriers; it does not say they fail to surround plaques, or isolate the finding to R47H. It discusses more diffuse, filamentous plaques and neurite damage in related comparisons, but does not report that these carriers had increased filamentous deposits and phospho-tau-positive neurites. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

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Authors
Nizami, S., Hall‐Roberts, H., Warrier, S., Cowley, S. A., & Di Daniel, E.
Affiliations
  • University of Oxford (GB)
  • Alzheimer's Research UK Oxford Drug Discovery Institute, Nuffield Department of Medicine University of Oxford Oxford UK
Corresponding author
Nizami, Sohaib
ORCID
Venue
British Journal of Pharmacology
Publisher
Wiley
Published
2019-05-11
Volume
176
Issue
18
Pages
3515-3532
ISSN
  • 0007-1188 (ISSN-L)
  • 1476-5381
DOI
10.1111/bph.14618
PMC
PMC6715590
OpenAlex
W2914464117
Cited by
147
References
158
Citations by year
2026: 16 · 2025: 18 · 2024: 19 · 2023: 18 · 2022: 27 · 2021: 24 · 2020: 19 · 2019: 5
FWCI
1.98
Type
journal article
Language
en
Open access
Licence
Locations
  • British Journal of Pharmacology (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
  • Medical Research Council (MC_EX_MR/N50192X/1)
  • Janssen Pharmaceuticals
Topics
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Inflammasome and immune disorders
Keywords
Alzheimer's disease, microglia, neuroinflammation, phagocytosis, NLRP3 inflammasome, complement system, TREM2, disease-modifying therapy, therapeutic target, microglial homeostasis
MeSH terms
NLR Family, Pyrin Domain-Containing 3 Protein, Alzheimer Disease, Animals, Complement System Proteins, Humans, Inflammation, Membrane Glycoproteins, Phagocytosis, Receptors, Immunologic, Microglia

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