Unraveling α-synuclein and amylin co-aggregation: pathological insights and biomarker development for Parkinson's disease
<b>Background:</b> Patients with diabetes have a higher morbidity in Parkinson's disease (PD) than others, but the mechanism underlying this link remains controversial. The co-aggregation of α-synuclein (α-syn) and amylin has been hypothesized as a key contributor. <b>Methods:</b> Molecular interaction analysis and co-immunoprecipitation were conducted to assess the feasibility of co-aggregation. We developed a tailored surface-based fluorescence distribution method to detect the co-aggregate in the subject's serum sample and brain-derived L1CAM-positive Extracellular Vesicles. Subjects include Health Controls (HC), PD patients and multiple system atrophy (MSA) patients. <b>Results:</b> The co-aggregates were detected in PD patient samples, in both serum and brain-derived extracellular vesicles (EVs). We demonstrated that the co-aggregate count could distinguish PD patients from healthy individuals. Our results revealed a positive correlation between co-aggregate count and Parkinson's disease scales or diabetes markers, highlighting the role of co-aggregation in promoting PD progression. The distribution of co-aggregates demonstrated diversity among different α-synucleinopathies; a high co-aggregates count was found in EVs and serum of PD patients, but not in the serum of MSA patients. <b>Conclusion:</b> The existence of α-syn-amylin co-aggregates was confirmed. Our findings suggest that α-syn-amylin co-aggregation may play a pivotal role in PD pathology, and have the potential as a biomarker. These results point to a potential path for early-diagnosis and therapeutic intervention.
Authors
- Minseok Kang (ORCID: https://orcid.org/0000-0003-4901-4465)
- Jianhe Guo
- Bowen Shu (ORCID: https://orcid.org/0000-0002-9704-2471)
- Keying Guo (ORCID: https://orcid.org/0000-0001-6383-6321)
- Yong Zhao (ORCID: https://orcid.org/0000-0003-4564-1912)
- Minchao Lai
- Rocky S. Tuan (ORCID: https://orcid.org/0000-0001-6067-6705)
- Bo Wang (ORCID: https://orcid.org/0000-0002-3231-1167)
- Dongjie Hu
- Renzhi Wang (ORCID: https://orcid.org/0000-0003-2080-5474)
- Zhong Alan Li (ORCID: https://orcid.org/0000-0002-6009-629X)
- Mingyuan Li (ORCID: https://orcid.org/0000-0002-9371-4613)
- Bo Li (ORCID: https://orcid.org/0000-0001-6824-4907)
- Dian Wang (ORCID: https://orcid.org/0000-0001-6125-8505)
- Chenzhong Li (ORCID: https://orcid.org/0000-0002-0486-4530)
- Jiang Cheng
- Yuhang Zhou (ORCID: https://orcid.org/0009-0006-6296-5328)
- Cheng Zhu (ORCID: https://orcid.org/0000-0002-7256-672X)
- Haoran Liu (ORCID: https://orcid.org/0009-0006-7570-4389)
Institutions
- Sun Yat-sen University (CN)
- Technion – Israel Institute of Technology (IL)
- Chinese University of Hong Kong (HK)
- Harbin Institute of Technology (CN)
- Shantou University (CN)
- First Affiliated Hospital of Shantou University Medical College (CN)
- Chinese University of Hong Kong, Shenzhen (CN)
- Shantou University Medical College (CN)
- Guangdong Technion-Israel Institute of Technology (CN)
- University of Hong Kong - Shenzhen Hospital (CN)
- Heilongjiang Institute of Technology (CN)
- Shenzhen Second People's Hospital (CN)
- Monash University (AU)
- Southern Medical University (CN)
- Monash Institute of Medical Research (AU)
Publication Details
- Journal
- Theranostics
- Published
- 2025-06-20
- DOI
- https://doi.org/10.7150/thno.112396
- Citations
- 3
- Primary Topic
- Parkinson's Disease Mechanisms and Treatments
- Type
- article
- Field-Weighted Citation Impact
- 4.17
Funders
- National Natural Science Foundation of China