The Role of Microglia in Antibody-Mediated Clearance of Amyloid-Beta from the Brain
Abstract
Immunotherapy has emerged as a leading new approach to the reduction of amyloid deposits in the brains of Alzheimer patients. At least 4 distinct actions of anti-Abeta antibodies have been proposed as contributing to the inhibition of amyloid deposition and its clearance. Critically, each of these proposed mechanisms may be acting simultaneously, and it is feasible that different antibodies may utilize each mechanism to a different extent. One of these proposed mechanisms involves the activation of microglia and the phagocytosis of Abeta peptide. In general this is assumed to proceed through the Fcgamma-receptor binding by antibody opsonized Abeta aggregates, however modifying the microglial phenotype into one with a greater propensity for phagocytosing Abeta is also feasible, as microglia avidly phagocytose Abeta in vitro without antibody present. Evidence is presented supporting arguments that microglial activation does play a role in amyloid removal, particularly compacted amyloid deposits, under certain conditions. In addition to the specific antibody used, other considerations in comparing different reports of antibody action in APP mice include the age of the mice, the extent of pre-existing amyloid when therapy is initiated, the time point when the effects of the therapy are examined and the route of antibody administration. Future questions will consider the source of the activated microglia near the plaques after antibody administration (resident or peripheral) and t…
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Microglial cells play pivotal role in maintaining immunoproteostasis through phagocytosis and degradation of misfolded proteins, their protective function is inseparably associated with immune activation exerting a chronic, potentially harmful effect on the regional milieu of neuronal networks.
“Though microglial cells play pivotal role in maintaining immunoproteostasis through phagocytosis and degradation of misfolded proteins, their protective function is inseparably associated with immune activation exerting a chronic, potentially harmful effect on the regional milieu of neuronal networks [35, 37–39].”
From APOE Genotype Differentially Modulates Effects of Anti-Aβ, Passive Immunization in APP Transgenic Mice (2017) · cites this paper as [39]
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- Authors
- Morgan, D.
- Venue
- CNS & Neurological Disorders - Drug Targets
- Publisher
- Bentham Science Publishers Ltd.
- Published
- 2009-03-01
- Volume
- 8
- Issue
- 1
- Pages
- 7-15
- ISSN
- 1568-007X (ISSN-L)
- 1871-5273
- OpenAlex
- W2077816165
- Cited by
- 58
- References
- 0
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 3 · 2023: 1 · 2022: 1 · 2021: 2 · 2020: 2 · 2019: 2 · 2018: 2 · 2017: 4 · 2016: 3 · 2015: 5 · 2014: 2 · 2013: 4 · 2012: 8
- FWCI
- 5.32
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- CNS & Neurological Disorders - Drug Targets (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Institute on Aging (AG25509, R01AG018478, AG 15490, R01 AG 18478, AG04418, P01AG004418, R01AG025509, AG 25711, R01AG015490, P50AG025711)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Neurology › Intracerebral and Subarachnoid Hemorrhage Research
- Keywords
- microglia, amyloid-beta clearance, anti-amyloid antibodies, Alzheimer's disease, antibody immunotherapy, microglial activation, phagocytosis, Fc gamma receptor, APP transgenic mice, microglial phenotype, amyloid plaques
- MeSH terms
- Alzheimer Disease, Animals, Antibodies, Humans, Immunotherapy, Phagocytosis, Amyloid beta-Peptides, Microglia, Mice
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