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

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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

DOI 10.1073/pnas.0904532106PMC PMC2836607

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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)
ORCID: Friedrich, Ralf P.
Westermann, Martin
Kaether, Christoph
Fändrich, Marcus
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
DOI: 10.1073/pnas.0904532106
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: Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › 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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Mechanism of amyloid plaque formation suggests an intracellular basis of Aβ pathogenicity

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