Ultrastructure of the microglia that phagocytose amyloid and the microglia that produce ?-amyloid fibrils
Abstract
The function of microglia associated with beta-amyloid deposits still remains a controversial issue. On the basis of recent ultrastructural data, microglia were postulated to be cells that form amyloid fibrils, not phagocytes that remove amyloid deposits. In this electron microscopic study, we examined the ability of microglia to ingest and digest exogenous amyloid fibrils in vitro. We demonstrate that amyloid fibrils are ingested by cultured microglial cells and collected and stored in phagosomes. The ingested, nondegraded amyloid remains within phagosomes for up to 20 days, suggesting a very limited effectiveness of microglia in degrading beta-amyloid fibrils. On the other hand, we showed that in microglial cells of classical plaques in brain cortex of patients with Alzheimer's disease, amyloid fibrils appear first in altered endoplasmic reticulum and deep infoldings of cell membranes. These differences in intracellular distribution of amyloid fibrils in microglial cells support our observations that microglial cells associated with amyloid plaques are engaged in production of amyloid, but not in phagocytosis.
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Microglia can engulf amyloid-β and sequester it in endosome-like compartments.
“Early ultrastructural studies in human brain specimens suggested that microglia can engulf amyloid-β (Aβ) and sequester it in endosome-like compartments (7).”
From Attenuating astrocyte activation accelerates plaque pathogenesis in APP/PS1 mice (2013) · cites this paper as [7]
At early time points after infusion, a substantial number of Aβ deposits are observed inside microglia within vesicular compartments consistent with phagolysosomes.
“However, at this early time point a substantial number of deposits were already observed inside microglia within vesicular compartments consistent with phagolysosomes(Frackowiak et al., 1992) (Figure 4A, C and supplementary movie 1).”
From CX3CR1 in Microglia Regulates Brain Amyloid Deposition through Selective Protofibrillar Amyloid-β Phagocytosis (2010) · cites this paper as Frackowiak et al., 1992
Microglial phagocytosis is believed to be dysfunctional in AD.
“Microglial phagocytosis is believed to be dysfunctional in AD [17–19].”
From IL-1β-driven amyloid plaque clearance is associated with an expansion of transcriptionally reprogrammed microglia (2019) · cites this paper as [17]
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- Authors
- Frackowiak, J., Wisniewski, H. M., Wegiel, J., Merz, G. S., Iqbal, K., & Wang, K. C.
- Venue
- Acta Neuropathologica
- Published
- 1992-08
- Volume
- 84
- Issue
- 3
- Pages
- 225-33
- ISSN
- 0001-6322 (ISSN-L)
- 1432-0533
- OpenAlex
- W2045720033
- Cited by
- 276
- References
- 4
- Citations by year
- 2026: 2 · 2025: 8 · 2024: 5 · 2023: 6 · 2022: 9 · 2021: 8 · 2020: 10 · 2019: 12 · 2018: 3 · 2017: 9 · 2016: 3 · 2015: 11 · 2014: 11 · 2013: 6 · 2012: 7
- 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 Institute on Aging (AGO-5892, P01 AGO-4220)
- 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, amyloid-beta, phagosome, amyloid plaques, Alzheimer's disease, endoplasmic reticulum
- MeSH terms
- Amyloid, Animals, Brain, Dogs, Immunohistochemistry, Neurofibrils, Neuroglia, Phagocytosis, Amyloid beta-Peptides, Culture Techniques
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