The role of microglial cells and astrocytes in fibrillar plaque evolution in transgenic APPSW mice
Abstract
Ultrastructural reconstruction of 27 fibrillar plaques in different stages of formation and maturation was undertaken to characterize the development of fibrillar plaques in the brains of human APP(SW) transgenic mice (Tg2576). The study suggests that microglial cells are not engaged in Abeta removal and plaque degradation, but in contrast, are a driving force in plaque formation and development. Fibrillar Abeta deposition at the amyloid pole of microglial cells appears to initiate three types of neuropil response: degeneration of neurons, protective activation of astrocytes, and attraction and activation of microglial cells sustaining plaque growth. Enlargement of neuronal processes and synapses with accumulation of degenerated mitochondria, dense bodies, and Hirano-type bodies is the marker of toxic injury of neurons by fibrillar Abeta. Separation of amyloid cores from neurons and degradation of amyloid cores by cytoplasmic processes of hypertrophic astrocytes suggest the protective and defensive character of astrocytic response to fibrillar Abeta. The growth of cored plaque from a small plaque with one microglial cell with an amyloid star and a few dystrophic neurites to a large plaque formed by several dozen microglial cells seen in old mice is the effect of attraction and activation of microglial cells residing outside of the plaque perimeter. This mechanism of growth of plaques appears to be characteristic of cored plaques in transgenic mice. Other features in mouse mic…
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Ultrastructural studies have shown that astrocytic invasion of plaques is associated with fragmentation of amyloid.
“Furthermore, ultrastructural studies have shown that astrocytic invasion of plaques is associated with fragmentation of amyloid (56, 59).”
From Attenuating astrocyte activation accelerates plaque pathogenesis in APP/PS1 mice (2013) · cites this paper as [56]
In brain specimens from patients with AD, activated astrocytes are intimately associated with amyloid plaques.
“In brain specimens from patients with AD, activated astrocytes are intimately associated with amyloid plaques (54–56)”
From Attenuating astrocyte activation accelerates plaque pathogenesis in APP/PS1 mice (2013) · cites this paper as [56]
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- Authors
- Wegiel, J.
- Venue
- Neurobiology of Aging
- Publisher
- Elsevier BV
- Published
- 2001-01
- Volume
- 22
- Issue
- 1
- Pages
- 49-61
- ISSN
- 0197-4580 (ISSN-L)
- OpenAlex
- W2015867258
- Cited by
- 159
- References
- 8
- Citations by year
- 2026: 5 · 2025: 7 · 2024: 2 · 2023: 5 · 2022: 4 · 2021: 4 · 2020: 1 · 2019: 6 · 2018: 3 · 2016: 10 · 2015: 6 · 2014: 8 · 2013: 3 · 2012: 13
- FWCI
- 4.71
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neurobiology of Aging (publishedVersion)
- PubMed (publishedVersion)
- 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 cells, astrocytes, amyloid plaques, Tg2576 mice, plaque formation, plaque maturation, amyloid core, lysosomal vacuoles, microglial activation, astrocytic response, neurodegeneration, Alzheimer's disease
- MeSH terms
- Alzheimer Disease, Amyloidosis, Animals, Astrocytes, Humans, Hypertrophy, Mice, Transgenic, Microscopy, Electron, Peptide Fragments, Synapses, Amyloid beta-Peptides, Amyloid beta-Protein Precursor, Microglia, Mice, Plaque, Amyloid
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