The DOI matches its Crossref record; 70 of the 70 references it cites were found in a registry or an index.
Differential Relationships of Reactive Astrocytes and Microglia to Fibrillar Amyloid Deposits in Alzheimer Disease
Open accessAbstract
Although it is clear that astrocytes and microglia cluster around dense-core amyloid plaques in Alzheimer disease (AD), whether they are primarily attracted to amyloid deposits or are just reacting to plaque-associated neuritic damage remains elusive. We postulate that astrocytes and microglia may differentially respond to fibrillar amyloid β. Therefore, we quantified the size distribution of dense-core thioflavin-S (ThioS)-positive plaques in the temporal neocortex of 40 AD patients and the microglial and astrocyte responses in their vicinity (≤50 μm) and performed correlations between both measures. As expected, both astrocytes and microglia were clearly spatially associated with ThioS-positive plaques (p = 0.0001, ≤50 μm vs. >50 μm from their edge), but their relationship to ThioS-positive plaque size differed: larger ThioS-positive plaques were associated with more surrounding activated microglia (p = 0.0026), but this effect was not observed with reactive astrocytes. Microglial response to dense-core plaques seems to be proportional to their size, which we postulate reflects a chemotactic effect of amyloid β. By contrast, plaque-associated astrocytic response does not correlate with plaque size and seems to parallel the behavior of plaque-associated neuritic damage.
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“Microglial and astrocytic interactions with Aβ amyloid plaques have been associated with amyloid plaque development and neuritic damage [81].”
From Enhanced microglial dynamics and a paucity of tau seeding in the amyloid plaque microenvironment contribute to cognitive resilience in Alzheimer’s disease (2024) · cites this paper as [81]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
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“One study showed that reactive astrocytes and activated microglia respond differently to Aβ plaque formation; while microglia respond directly to the presence of plaques, astrocytes are associated with neuritic damage that occurs when synapses are already dysfunctional [81].”
From Enhanced microglial dynamics and a paucity of tau seeding in the amyloid plaque microenvironment contribute to cognitive resilience in Alzheimer’s disease (2024) · cites this paper as [81]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
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“These results are consistent with a dynamic phenotypic change of astrocytes from homeostatic to reactive through an intermediate state in response to their microenvironment conditions, namely the presence of Aβ plaques and NFTs23,54–57”
From Astrocyte transcriptomic changes along the spatiotemporal progression of Alzheimer’s disease (2024) · cites this paper as [55]
Experimental — accuracy not yet measuredIn the citing paper
“In the brains of AD patients and APP-overexpressing mice, plaques are surrounded by reactive microglia and astrocytes (Meyer-Luehmann et al., 2008; Serrano-Pozo et al., 2013)”
From NHE6 depletion corrects ApoE4-mediated synaptic impairments and reduces amyloid plaque load (2021) · cites this paper as Serrano-Pozo et al., 2013
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Self-citationRAGE and amyloid-β peptide neurotoxicity in Alzheimer's disease
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Microglia-specific localisation of a novel calcium binding protein, Iba1
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Self-citationMicroglial Dysfunction and Defective β-Amyloid Clearance Pathways in Aging Alzheimer's Disease Mice
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Metadata
- Authors
- Serrano-Pozo, A., Muzikansky, A., Gómez-Isla, T., Growdon, J. H., Betensky, R. A., Frosch, M. P., & Hyman, B. T.
- Affiliations
- Massachusetts General Hospital (US)
- Harvard University (US)
- Corresponding author
- Hyman, Bradley T.
- Venue
- Journal of Neuropathology & Experimental Neurology
- Publisher
- Oxford University Press (OUP)
- Published
- 2013-06
- Volume
- 72
- Issue
- 6
- Pages
- 462-471
- ISSN
- 0022-3069 (ISSN-L)
- 1554-6578
- PMC
- PMC3661683
- OpenAlex
- W1995111570
- Cited by
- 226
- References
- 70
- Citations by year
- 2026: 14 · 2025: 25 · 2024: 21 · 2023: 22 · 2022: 22 · 2021: 25 · 2020: 14 · 2019: 22 · 2018: 20 · 2017: 10 · 2016: 8 · 2015: 16 · 2014: 5 · 2013: 2
- FWCI
- 7.19
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- public-domain
- Locations
- Journal of Neuropathology & Experimental Neurology (publishedVersion, public-domain)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Massachusetts General Hospital
- National Institutes of Health (AG08487)
- National Institute on Aging (AG008487, R01AG008487, P50AG005134, P30AG062421)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › 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 plaques, reactive astrocytes, microglial activation, fibrillar amyloid-beta, plaque size, thioflavin S, temporal neocortex, chemotaxis
- MeSH terms
- Aged, Aged, 80 and over, Alzheimer Disease, Astrocytes, Brain, Female, Humans, Male, Microglia, Plaque, Amyloid
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