Α-synuclein aggregation is triggered by oligomeric amyloid-β 42 via heterogeneous primary nucleation
File(s)
Published version
Author(s)
Type
Journal Article
Abstract
An increasing number of cases where amyloids of different proteins are found in the same patient are being
reported. This observation complicates diagnosis and clinical intervention. Amyloids of the amyloid-β peptide or the protein
α-synuclein are traditionally considered hallmarks of Alzheimer’s and Parkinson’s diseases, respectively. However, the cooccurrence of amyloids of these proteins has also been reported in patients diagnosed with either disease. Here, we show that
soluble species containing amyloid-β can induce the aggregation of α-synuclein. Fibrils formed under these conditions are
solely composed of α-synuclein to which amyloid-β can be found associated, but not as part of the core of the fibrils. Importantly, by global kinetic analysis, we found that the aggregation of α-synuclein under these conditions occurs via heterogeneous primary nucleation, triggered by soluble aggregates containing amyloid-β.
reported. This observation complicates diagnosis and clinical intervention. Amyloids of the amyloid-β peptide or the protein
α-synuclein are traditionally considered hallmarks of Alzheimer’s and Parkinson’s diseases, respectively. However, the cooccurrence of amyloids of these proteins has also been reported in patients diagnosed with either disease. Here, we show that
soluble species containing amyloid-β can induce the aggregation of α-synuclein. Fibrils formed under these conditions are
solely composed of α-synuclein to which amyloid-β can be found associated, but not as part of the core of the fibrils. Importantly, by global kinetic analysis, we found that the aggregation of α-synuclein under these conditions occurs via heterogeneous primary nucleation, triggered by soluble aggregates containing amyloid-β.
Date Issued
2023-08-23
Date Acceptance
2023-07-17
Citation
Journal of the American Chemical Society, 2023, 145 (33), pp.18276-18285
ISSN
0002-7863
Publisher
American Chemical Society
Start Page
18276
End Page
18285
Journal / Book Title
Journal of the American Chemical Society
Volume
145
Issue
33
Copyright Statement
Copyright © 2022 The Authors. Published by American Chemical Society. This publication is licensed under
CC-BY 4.0.
CC-BY 4.0.
License URL
Identifier
https://pubs.acs.org/doi/full/10.1021/jacs.3c03212
Publication Status
Published
Date Publish Online
2023-08-09