Work

Unraveling α-synuclein and amylin co-aggregation: pathological insights and biomarker development for Parkinson's disease

Year: 2025

Type: article

Abstract: Background: 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.Methods: 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.Results: 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. Conclusion: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.

Source: Theranostics

DOI: 10.7150/thno.112396