Kinetic theory of fibrillogenesis of amyloid β-protein
Open accessAbstract
Prior quasielastic light scattering (QLS) studies of fibrillogenesis of synthetic amyloid beta-protein (Abeta)-(1-40) at low pH have suggested a kinetic model in which: (i) fibrillogenesis requires a nucleation step; (ii) nuclei are produced by Abeta micelles in addition to seeds initially present; and (iii) fibril elongation occurs by irreversible binding of Abeta monomers to the fibril ends. Here we present the full mathematical formulation of this model. We describe the temporal evolution of the concentrations of Abeta monomers and micelles as well as the concentration and size distribution of fibrils. This formulation enables deduction of the fundamental parameters of the model-e.g., the nucleation and elongation rate constants kn and ke-from the time dependency of the apparent diffusion coefficient measured by QLS. The theory accurately represents the experimental observations for Abeta concentrations both below and above c*, the critical concentration for Abeta micelle formation. We suggest that the method of QLS in combination with this theory can serve as a powerful tool for understanding the molecular factors that control Abeta plaque formation.
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The concentration of Aβ is a critical factor determining if and when it will aggregate into toxic structures.
“The concentration of Aβ is a critical factor determining if and when it will aggregate into these toxic structures; high concentrations of Aβ are more prone to convert from its normal soluble form into these multimeric conformations (3).”
From Serotonin signaling is associated with lower amyloid-β levels and plaques in transgenic mice and humans (2011) · cites this paper as [3]
High concentrations of Aβ are more prone to convert from its normal soluble form into multimeric conformations.
“The concentration of Aβ is a critical factor determining if and when it will aggregate into these toxic structures; high concentrations of Aβ are more prone to convert from its normal soluble form into these multimeric conformations (3).”
From Serotonin signaling is associated with lower amyloid-β levels and plaques in transgenic mice and humans (2011) · cites this paper as [3]
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- Authors
- Lomakin, A., Teplow, D. B., Kirschner, D. A., & Benedek, G. B.
- Affiliations
- Boston College (US)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 1997-07-22
- Volume
- 94
- Issue
- 15
- Pages
- 7942-7947
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC21534
- OpenAlex
- W2090235059
- Cited by
- 529
- References
- 1
- Citations by year
- 2026: 4 · 2025: 4 · 2024: 9 · 2023: 6 · 2022: 7 · 2021: 17 · 2020: 19 · 2019: 16 · 2018: 20 · 2017: 22 · 2016: 23 · 2015: 17 · 2014: 25 · 2013: 24 · 2012: 37
- FWCI
- 5.49
- 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)
- Funders
- National Institutes of Health (5p01ag014366-05)
- National Institute on Aging (1PO1 AG14366)
- National Eye Institute (R37EY005127, 5R37EY05127)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Prion Diseases and Protein Misfolding
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Keywords
- amyloid-beta, fibril formation, nucleation, fibril elongation, kinetic model, dynamic light scattering, apparent diffusion coefficient, critical concentration, Alzheimer's disease, amyloid plaques
- MeSH terms
- Kinetics, Models, Chemical, Neurofibrils, Scattering, Radiation, Spectrum Analysis, Amyloid beta-Peptides
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