Modulation of β-Amyloid Fibril Formation in Alzheimer’s Disease by Microglia and Infection
Open accessAbstract
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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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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Why are Functional Amyloids Non-Toxic in Humans?
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Degradation of fibrillar forms of Alzheimer's amyloid β-peptide by macrophages
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Efficacy and Safety of a Brain-Penetrant Biologic TNF-α Inhibitor in Aged APP/PS1 Mice
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TLR4/Rac1/NLRP3 Pathway Mediates Amyloid-β-Induced Neuroinflammation in Alzheimer’s Disease
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Neuroprotective insights into epigallocatechin gallate (EGCG) for neurodegenerative disorders
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N‑terminal Domain of Amyloid‑β Impacts Fibrillation and Neurotoxicity
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Rational design of photoactivatable metal complexes to target and modulate amyloid-β peptides
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Heparin-Assisted Amyloidogenesis Uncovered through Molecular Dynamics Simulations
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Shifting Microglial Phenotypes: Targeting Disease-Associated Microglia in Neurodegeneration
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Coupling of Alzheimer’s Disease Genetic Risk Factors with Viral Susceptibility and Inflammation
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Spatiotemporally Traceable Peptide Self-Assemblies for Mitochondrial-Specific Dysfunction
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Unveiling the biological interface of protein complexes by mass spectrometry‐coupled methods
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Translational control of microglial inflammatory and neurodegenerative responsesPreprint
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Neuroglia targeting nano-therapeutic approaches to rescue aging and neurodegenerating brain
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Amyloid fibril cytotoxicity and associated disorders
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Molecular reflection of the mind: Exosomes in major depressive disorder
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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
- Publisher
- Frontiers Media SA
- Published
- 2020-11-26
- Volume
- 13
- Pages
- 609073-609073
- ISSN
- 1662-5099 (ISSN-L)
- PMC
- PMC7725705
- 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
- gold
- doi.org
- Licence
- 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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