Cited by 303Alzheimer's disease research and treatmentsNeuroinflammation and Neurodegeneration MechanismsDementia and Cognitive Impairment Research

Mechanism of amyloid plaque formation suggests an intracellular basis of Aβ pathogenicity

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Friedrich, Ralf P., Tepper, Katharina, Rönicke, Raik, Soom, Malle, Westermann, Martin, Reymann, Klaus, Kaether, Christoph, Fändrich, Marcus·2010·Proceedings of the National Academy of Sciences

Abstract

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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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
Published
2010-01-19
Volume
107
Issue
5
Pages
1942-1947
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
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
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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