PT  - JOURNAL ARTICLE
AU  - Devkee M. Vadukul
AU  - Rebecca J. Thrush
AU  - Yiyun Jin
AU  - Francesco A. Aprile
TI  - Amyloid-β Oligomers Serve as Nucleation Sites for α-Synuclein Aggregation
AID  - 10.1101/2022.06.20.496547
DP  - 2022 Jan 01
TA  - bioRxiv
PG  - 2022.06.20.496547
4099  - http://biorxiv.org/content/early/2022/06/20/2022.06.20.496547.short
4100  - http://biorxiv.org/content/early/2022/06/20/2022.06.20.496547.full
AB  - Neurodegenerative diseases are associated with the formation of amyloids in the nervous system. An increasing number of cases where amyloids of the same protein are found in different dementias is 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 co-occurrence of amyloids of these proteins has also been reported in patients diagnosed with either disease. Here, we provide new evidence about the protein composition of aggregates formed when these two proteins are co-present. We show that soluble species of amyloid-β can induce the aggregation of α-synuclein. The amyloid 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. Our data take us one step closer to understanding the complex nature of heterogenous aggregation in disease contexts which may aid clinical diagnosis and the development of therapeutic interventions.Significance statement Aggregates of both the amyloid-β peptide and α-synuclein have been detected in up to 50% of patients diagnosed with either Alzheimer’s or Parkinson’s diseases. This observation has raised several questions on how the two proteins influence each other’s aggregations. Recently, it has been shown that amyloid-β and α-synuclein can co-aggregate. Here, we further clarify this process. We show that amyloid-β can trigger the aggregation of α-synuclein but is not present in the core of the resulting aggregates. This mechanism is a specific property of the soluble species of amyloid-β but not of the insoluble fibrillar aggregates. Our findings indicate that aggregation amyloid-β–α-synuclein co-incubation is a consequence of the property of amyloid-β to serve as nucleation interface for α-synuclein aggregation.Competing Interest StatementThe authors have declared no competing interest.