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Updated: Jun 1, 2026
Analysis of β-Amyloid-induced Abnormalities on Fibrin Clot Structure by Spectroscopy and Scanning Electron Microscopy
Published on: November 30, 2018
Evaluating nuclei concentration in amyloid fibrillation reactions using back-calculation approach
Mirco Sorci1, Whitney Silkworth, Timothy Gehan
1Howard P. Isermann Department of Chemical and Biological Engineering and Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, New York, United States of America.
Researchers estimated the concentration of amyloid nuclei, crucial in protein aggregation, to be in the picomolar range. This low concentration may explain the difficulty in targeting amyloid toxicity and the slow progression of amyloid diseases.
Area of Science:
- Biochemistry
- Molecular Biology
- Neuroscience
Background:
- Over 20 proteins are linked to amyloid diseases, yet the mechanisms of amyloid toxicity and inhibition remain unclear.
- Conflicting reports exist regarding whether amyloid fibrils or their oligomeric precursors are toxic.
- Quantifying the temporal concentration of these species may enhance understanding of amyloid aggregation.
Purpose of the Study:
- To estimate the in vitro concentration of amyloid nuclei.
- To correlate nuclei concentration with amyloid aggregation and disease onset.
Main Methods:
- Utilized a back-calculation method based on nucleation events in protein-to-fibril conversion.
- Modeled the process using recombinant human insulin as a model hormone.
Main Results:
- Estimated the in vitro concentration of amyloid nuclei to be in the picomolar range.
- This estimate is conservative, as fibril fragmentation was not included and would lower nuclei concentration.
Conclusions:
- The very low concentration of amyloid nuclei and oligomers could explain challenges in isolating and blocking their toxicity.
- This low concentration may also contribute to the long onset times observed in amyloid diseases.
