Cited by 67Alzheimer's disease research and treatmentsNeuroinflammation and Neurodegeneration MechanismsDementia and Cognitive Impairment Research

Modulation of β-Amyloid Fibril Formation in Alzheimer’s Disease by Microglia and Infection

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Brown, Madeleine R., Radford, Sheena E., Hewitt, Eric W.·2020·Frontiers in Molecular Neuroscience

Abstract

Amyloid plaques are a pathological hallmark of Alzheimer’s disease. The major component of these plaques are highly ordered amyloid fibrils formed by amyloid-β (Aβ) peptides. However, whilst Aβ amyloid fibril assembly has been subjected to detailed and extensive analysis in vitro, these studies may not reproduce how Aβ fibrils assemble in the brain. This is because the brain represents a highly complex and dynamic environment, and in Alzheimer’s disease multiple cofactors may affect the assembly of Aβ fibrils. Moreover, in vivo amyloid plaque formation will reflect the balance between the assembly of Aβ fibrils and their degradation. This review explores the roles of microglia as cofactors in Aβ aggregation and in the clearance of amyloid deposits. In addition, we discuss how infection may be an additional cofactor in Aβ fibril assembly by virtue of the antimicrobial properties of Aβ peptides. Crucially, by understanding the roles of microglia and infection in Aβ amyloid fibril assembly it may be possible to identify new therapeutic targets for Alzheimer’s disease.

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Crossref · 10.3389/fnmol.2020.609073

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  • Microglia are required for the consolidation of neurotoxic soluble Aβ oligomers into more inert insoluble fibrils and for construction into compact plaques.

    “Microglia are required for the consolidation of neurotoxic soluble Aβ oligomers into more inert insoluble fibrils and for construction into compact plaques (Brown et al., 2020; Huang et al., 2021; Martin et al., 1994).”

    From SYK coordinates neuroprotective microglial responses in neurodegenerative disease (2022) · cites this paper as Brown et al., 2020

    The ‘Formation of Physical Barriers Around Aβ Amyloid Plaques by Microglia’ section (page unavailable) says microglia compact plaque cores; plaques with less microglial coverage were less compact and had more neurotoxic protofibrillar hotspots. It does not establish that microglia are required to convert soluble Aβ oligomers into insoluble fibrils, or that the resulting fibrils are inert. (LLM, conf=0.87)

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Authors
Brown, M. R., Radford, S. E., & Hewitt, E. W.
Affiliations
University of Leeds (GB)
Corresponding author
Hewitt, Eric W.
Venue
Frontiers in Molecular Neuroscience
Published
2020-11-26
Volume
13
Pages
609073-609073
ISSN
1662-5099 (ISSN-L)
OpenAlex
W3108115027
Cited by
67
References
180
Citations by year
2026: 8 · 2025: 10 · 2024: 15 · 2023: 19 · 2022: 11 · 2021: 4
FWCI
1.08
Type
journal article
Language
en
Open access
Locations
  • Frontiers in Molecular Neuroscience (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • White Rose Research Online (University of Leeds, The University of Sheffield, University of York) (acceptedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • Wellcome Trust (204963)
  • Medical Research Council (MR/N013840/1)
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
Keywords
Alzheimer's disease, amyloid-beta, amyloid fibril formation, microglia, amyloid plaques, infection, amyloid clearance, therapeutic target

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