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bioRxiv · 10.1101/2022.06.20.496547

Amyloid-β Oligomers Serve as Nucleation Sites for α-Synuclein Aggregation

Vadukul, D. M.·Thrush, R. J.·Jin, Y.·Aprile, F. A.
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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-{beta} peptide or the protein -synuclein are traditionally considered hallmarks of Alzheimers and Parkinsons diseases, respectively. However, the co-occurrence of amyloids of these proteins has also been reported in patients diagnosed with either disease. Here, we show that soluble species containing amyloid-{beta} can induce the aggregation of -synuclein. Fibrils formed under these conditions are solely composed of -synuclein to which amyloid-{beta} 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 -synuclein under these conditions occurs via heterogeneous primary nucleation, triggered by soluble aggregates containing amyloid-{beta}.

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Vadukul, D. M., Thrush, R. J., Jin, Y., Aprile, F. A.. 2022-06-20. Amyloid-β Oligomers Serve as Nucleation Sites for α-Synuclein Aggregation. https://doi.org/10.1101/2022.06.20.496547

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