Association of Microglia with Amyloid Plaques in Brains of APP23 Transgenic Mice
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Microglia are a key component of the inflammatory response in the brain and are associated with senile plaques in Alzheimer's disease (AD). Although there is evidence that microglial activation is important for the pathogenesis of AD, the role of microglia in cerebral amyloidosis remains obscure. The present study was undertaken to investigate the relationship between beta-amyloid deposition and microglia activation in APP23 transgenic mice which express human mutated amyloid-beta precursor protein (betaPP) under the control of a neuron-specific promoter element. Light microscopic analysis revealed that the majority of the amyloid plaques in neocortex and hippocampus of 14- to 18- month-old APP23 mice are congophilic and associated with clusters of hypertrophic microglia with intensely stained Mac-1- and phosphotyrosine-positive processes. No association of such activated microglia was observed with diffuse plaques. In young APP23 mice, early amyloid deposits were already of dense core nature and were associated with a strong microglial response. Ultrastructurally, bundles of amyloid fibrils, sometimes surrounded by an incomplete membrane, were observed within the microglial cytoplasm. However, microglia with the typical characteristics of phagocytosis were associated more frequently with dystrophic neurites than with amyloid fibrils. Although the present observations cannot unequivocally determine whether microglia are causal, contributory, or consequential to cerebral amyloidosis, our results suggest that microglia are involved in cerebral amyloidosis either by participating in the processing of neuron-derived betaPP into amyloid fibrils and/or by ingesting amyloid fibrils via an uncommon phagocytotic mechanism. In any case, our observations demonstrate that neuron-derived betaPP is sufficient to induce not only amyloid plaque formation but also amyloid-associated microglial activation similar to that reported in AD. Moreover, our results are consistent with the idea that microglia activation may be important for the amyloid-associated neuron loss previously reported in these mice.
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Activated microglia surround amyloid plaques in human Alzheimer's disease and mouse Aβ amyloidosis models.
“Activated microglia surround amyloid plaques in the brains of both human patients with AD and mouse models of Aβ amyloidosis13,15,21,22.”
From Deletion of SPI1 in microglia exacerbates amyloid pathology by impairing microglial response in Alzheimer’s disease models (2026) · cites this paper as [22]
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Self-citation
- Authors
- Stalder, M., Phinney, A., Probst, A., Sommer, B., Staufenbiel, M., & Jucker, M.
- Affiliations
- University of Basel (CH)
- Novartis (Switzerland) (CH)
- Corresponding author
- Jucker, Mathias
- Venue
- The American Journal of Pathology
- Publisher
- Elsevier BV
- Published
- 1999-06
- Volume
- 154
- Issue
- 6
- Pages
- 1673-1684
- ISSN
- 0002-9440 (ISSN-L)
- PMC
- PMC1866618
- OpenAlex
- W2090811490
- Cited by
- 345
- References
- 48
- Citations by year
- 2026: 3 · 2025: 11 · 2024: 11 · 2023: 9 · 2022: 14 · 2021: 19 · 2020: 9 · 2019: 6 · 2018: 11 · 2017: 12 · 2016: 12 · 2015: 12 · 2014: 9 · 2013: 10 · 2012: 16
- FWCI
- 9.44
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- American Journal Of Pathology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Universität Basel
- Novartis Pharma
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Neuroscience › Neurology › Neurological Disease Mechanisms and Treatments
- Keywords
- microglial activation, amyloid plaques, APP23 transgenic mice, cerebral amyloidosis, Alzheimer's disease, amyloid-beta deposition, amyloid fibrils, phagocytosis, Mac-1, phosphotyrosine, hippocampus, neocortex, dystrophic neurites, neuroinflammation
- MeSH terms
- Animals, Brain, Congo Red, Immunohistochemistry, Male, Mice, Transgenic, Microscopy, Immunoelectron, Microglia, Mice, Plaque, Amyloid
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