Uptake, Degradation, and Release of Fibrillar and Soluble Forms of Alzheimer's Amyloid β-Peptide by Microglial Cells
Open accessAbstract
Microglia are phagocytic cells that are the main inflammatory response cells of the central nervous system. In Alzheimer's disease brain, activated microglia are concentrated in regions of compact amyloid deposits that contain the 39-43-amino acid Abeta peptide. We examined the uptake, degradation, and release of small aggregates of fibrillar Abeta (fAbeta) or soluble Abeta (sAbeta) by microglia. We found that although some degradation of fAbeta was observed over 3 days, no further degradation was observed over the next 9 days. Instead, there was a slow release of intact Abeta. The poor degradation was not due to inhibition of lysosomal function, since the rate of alpha2-macroglobulin degradation was not affected by the presence of fAbeta in the late endosomes/lysosomes. In contrast to fAbeta, internalization of sAbeta was not saturable. After internalization, sAbeta was released rapidly from microglia, and very little was degraded. These data show that fAbeta and sAbeta interact differently with microglia but that after internalization a large fraction of both are released without degradation.
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In the AD brain, microglia fail to effectively phagocytose Aβ and are impaired in their ability to degrade Aβ fibrils.
“In the AD brain, microglia fail to effectively phagocytose Aβ and are also impaired in their ability to degrade Aβ fibrils (Chung et al., 1999; Cameron and Landreth, 2010).”
From Mechanisms Underlying the Rapid Peroxisome Proliferator-Activated Receptor-γ-Mediated Amyloid Clearance and Reversal of Cognitive Deficits in a Murine Model of Alzheimer's Disease (2012) · cites this paper as Chung et al., 1999
The Abstract (page unavailable) reports that microglia took up fibrillar Aβ but degraded it only partly, then released intact Aβ. This supports poor degradation, not a failure to phagocytose Aβ. The study examined uptake and degradation by microglial cells; it does not establish that microglia in the AD brain are impaired in either ability. (LLM, conf=0.88)
Experimental — accuracy not yet measuredAβ, when endocytosed, becomes concentrated in acidic endosomal compartments, which promotes amyloid fibril formation and then secretion.
“Aβ, when endocytosed, becomes concentrated in the acidic endosomal compartments, which promotes amyloid fibril formation and then secretion (Chung et al, 1999; Hu et al, 2009; Knauer et al, 1992).”
From APOE from astrocytes restores Alzheimer’s Aβ-pathology and DAM-like responses in APOE deficient microglia (2024) · cites this paper as Chung et al, 1999
The Results report that internalized soluble Aβ concentrates in organelles consistent with late endosomes and lysosomes before release. The Discussion says low pH should promote fibril growth, but treats incorporation of soluble Aβ into fibrils as a possibility. The paper reports release of internalized Aβ, not that newly formed fibrils are subsequently secreted; the claim presents that sequence as established. (LLM, conf=0.87)
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- Authors
- Chung, H., Brazil, M. I., Soe, T. T., & Maxfield, F. R.
- Affiliations
- Cornell University (US)
- Corresponding author
- Maxfield, Frederick R.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 1999-11
- Volume
- 274
- Issue
- 45
- Pages
- 32301-32308
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2010464023
- Cited by
- 212
- References
- 14
- Citations by year
- 2026: 1 · 2025: 7 · 2024: 8 · 2023: 2 · 2022: 7 · 2021: 5 · 2020: 9 · 2019: 8 · 2018: 3 · 2017: 5 · 2016: 8 · 2015: 7 · 2014: 9 · 2013: 8 · 2012: 11
- FWCI
- 6.43
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Institute of Neurological Disorders and Stroke (R01NS034761, NS34761)
- 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
- Alzheimer's disease, amyloid-beta, microglia, fibrillar amyloid-beta, soluble amyloid-beta, peptide absorption, peptide degradation, peptide release, lysosomes, alpha2-macroglobulin, endocytosis, internalization, neuroinflammation
- MeSH terms
- Alzheimer Disease, Animals, Animals, Newborn, Cells, Cultured, Ligands, Lysosomes, Endosomes, Solubility, Amyloid beta-Peptides, Microglia, Mice
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