Mechanism of amyloid plaque formation suggests an intracellular basis of Aβ pathogenicity
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The formation of extracellular amyloid plaques is a common patho-biochemical event underlying several debilitating human conditions, including Alzheimer’s disease (AD). Considerable evidence implies that AD damage arises primarily from small oligomeric amyloid forms of Aβ peptide, but the precise mechanism of pathogenicity remains to be established. Using a cell culture system that reproducibly leads to the formation of Alzheimer’s Aβ amyloid plaques, we show here that the formation of a single amyloid plaque represents a template-dependent process that critically involves the presence of endocytosis- or phagocytosis-competent cells. Internalized Aβ peptide becomes sorted to multivesicular bodies where fibrils grow out, thus penetrating the vesicular membrane. Upon plaque formation, cells undergo cell death and intracellular amyloid structures become released into the extracellular space. These data imply a mechanism where the pathogenic activity of Aβ is attributed, at least in part, to intracellular aggregates.
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Endosomal Aβ42 labeling by immuno-EM has been confirmed by other groups.
“Endosomal Aβ42 labeling by immuno-EM has since been confirmed by other groups [49, 95, 143].”
From Intraneuronal β-amyloid accumulation and synapse pathology in Alzheimer’s disease (2010) · cites this paper as [49]
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Self-citation
- Authors
- Friedrich, R. P., Tepper, K., Rönicke, R., Soom, M., Westermann, M., Reymann, K., Kaether, C., & Fändrich, M.
- Affiliations
- Leibniz Institute on Aging - Fritz Lipmann Institute (FLI) (DE)
- Leibniz Institute for Neurobiology (DE)
- Friedrich Schiller University Jena (DE)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2010-01-19
- Volume
- 107
- Issue
- 5
- Pages
- 1942-1947
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC2836607
- OpenAlex
- W2036172794
- Cited by
- 303
- References
- 63
- Citations by year
- 2026: 12 · 2025: 13 · 2024: 20 · 2023: 20 · 2022: 13 · 2021: 21 · 2020: 23 · 2019: 11 · 2018: 30 · 2017: 28 · 2016: 15 · 2015: 18 · 2014: 8 · 2013: 24 · 2012: 13
- FWCI
- 15.38
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Informationszentrum Lebenswissenschaften (ZB MED) (submittedVersion)
- 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
- amyloid plaque formation, amyloid-beta, Alzheimer's disease, multivesicular bodies, endocytosis, phagocytosis, cell death, amyloid-beta oligomers
- MeSH terms
- Alzheimer Disease, Animals, Cell Line, Chlorocebus aethiops, Freeze Fracturing, Humans, Intracellular Fluid, Microscopy, Electron, Scanning, Peptide Fragments, Amyloid beta-Peptides, Microscopy, Video, COS Cells, Mice, Plaque, Amyloid
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