Microglial activation facilitates Aβ plaque removal following intracranial anti-Aβ antibody administration
Open accessAbstract
The mechanisms by which anti-Abeta antibodies clear amyloid plaques in Abeta depositing transgenic mice are unclear. In the current study, we demonstrate that inhibition of anti-Abeta antibody-induced microglial activation with anti-inflammatory drugs, such as dexamethasone, inhibits removal of fibrillar amyloid deposits. We also show that anti-Abeta F(ab')(2) fragments fail to activate microglia and are less efficient in removing fibrillar amyloid than the corresponding complete IgG. Diffuse Abeta deposits are cleared by antibodies under all circumstances. These data suggest that microglial activation is necessary for efficient removal of compact amyloid deposits with immunotherapy. Inhibition of this activation may result in an impaired clinical response to vaccination against Abeta.
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Anti-apoE antibody might modulate similar inflammatory responses, consistent with the effect of certain anti-Aβ antibodies.
“This finding suggests that anti-apoE antibody might modulate similar inflammatory responses, which is consistent with the effect of certain anti-Aβ antibodies (Bard et al., 2000; Wilcock et al., 2004).”
From Anti-apoE immunotherapy inhibits amyloid accumulation in a transgenic mouse model of Aβ amyloidosis (2012) · cites this paper as Wilcock et al., 2004
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Self-citation
- Authors
- Wilcock, D. M., Munireddy, S. K., Rosenthal, A., Ugen, K. E., Gordon, M. N., & Morgan, D.
- Affiliations
- University of South Florida (US)
- Venue
- Neurobiology of Disease
- Publisher
- Elsevier BV
- Published
- 2004-02
- Volume
- 15
- Issue
- 1
- Pages
- 11-20
- ISSN
- 0969-9961 (ISSN-L)
- OpenAlex
- W2063909850
- Cited by
- 202
- References
- 43
- Citations by year
- 2026: 7 · 2025: 15 · 2024: 8 · 2023: 3 · 2022: 3 · 2021: 6 · 2020: 7 · 2019: 2 · 2018: 4 · 2017: 3 · 2016: 2 · 2015: 12 · 2014: 6 · 2013: 11 · 2012: 12
- FWCI
- 8.07
- Type
- journal article
- Language
- en
- Open access
- green
- doaj.org
- Licence
- Locations
- Neurobiology of Disease (publishedVersion)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Institutes of Health
- National Institute on Aging (R01AG018478, AG 15490, R01AG020227, AG20227, R01AG015490, AG18478)
- 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
- microglial activation, amyloid plaques, plaque clearance, dexamethasone, anti-inflammatory agents, F(ab')2 fragments, Alzheimer's disease
- MeSH terms
- Alzheimer Disease, Animals, Anti-Inflammatory Agents, Antibodies, Brain, Dexamethasone, Disease Models, Animal, Encephalitis, Flurbiprofen, Gliosis, Immunoglobulin G, Mice, Transgenic, Peptide Fragments, Vaccines, Amyloid beta-Peptides, Leukocyte Common Antigens, Microglia, Mice, Plaque, Amyloid
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