Microglial cells are the driving force in fibrillar plaque formation, whereas astrocytes are a leading factor in plaque degradation
Abstract
Ultrastructural three-dimensional reconstruction of human classical plaques in different stages of development shows that microglial cells are the major factor driving plaque formation by fibrillar amyloid-beta (Abeta) deposition. The amount of fibrillar Abeta released by microglial cells and the area of direct contact between amyloid and neuron determine the extent of dystrophic changes in neuronal processes and synapses. The volume of hypertrophic astrocytic processes separating fibrillar amyloid from neuron is a measure of the protective activation of astrocytes. On the bases of the volume of amyloid star, microglial cells, dystrophic neurites, and hypertrophic astrocytic processes, and spatial relationships between plaque components, three stages in classical plaque development have been distinguished: early, mature, and late. In early plaque, the leading pathology is fibrillar Abeta deposition by microglial cells with amyloid star formation. The mature plaque is characterized by a balance between amyloid production, neuronal dystrophy, and astrocyte hypertrophy. In late classical plaque, microglial cells retract and expose neuropil on direct contact with amyloid star, enhancing both dystrophic changes in neurons and hypertrophic changes in astrocytes. In late plaques, activation of astrocytes predominates. They degrade amyloid star and peripheral amyloid wisps. The effect of these changes is classical plaque degradation to fibrillar primitive and finally to nonfibrillar,…
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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 [55]
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- Authors
- Wegiel, J., Wang, K. C., Tarnawski, M., & Lach, B.
- Affiliations
- Ottawa Hospital (CA)
- ORCID
- Venue
- Acta Neuropathologica
- Published
- 2000-10-28
- Volume
- 100
- Issue
- 4
- Pages
- 356-364
- ISSN
- 0001-6322 (ISSN-L)
- 1432-0533
- OpenAlex
- W2024304291
- Cited by
- 124
- References
- 6
- Citations by year
- 2026: 3 · 2025: 4 · 2024: 2 · 2023: 4 · 2022: 3 · 2021: 1 · 2020: 6 · 2019: 3 · 2018: 1 · 2017: 1 · 2016: 3 · 2015: 7 · 2014: 2 · 2013: 4 · 2012: 9
- FWCI
- 3.68
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Acta Neuropathologica (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Institute on Aging
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (P0Q-HD3897)
- Topics
- Health Sciences › Medicine › Physiology › 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
- microglia, astrocytes, amyloid plaques, dystrophic neurites, synaptic loss, astrocyte hypertrophy, Alzheimer's disease
- MeSH terms
- Aged, Alzheimer Disease, Astrocytes, Female, Humans, Hypertrophy, Male, Amyloid beta-Peptides, Neurites, Neurofibrillary Tangles, Microglia, Disease Progression, Plaque, Amyloid
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