Ultrasensitive detection of aggregated α-synuclein using quiescent seed amplification assay for the diagnosis of Parkinson’s disease

Autor: Hengxu Mao, Yaoyun Kuang, Du Feng, Xiang Chen, Lin Lu, Wencheng Xia, Tingting Gan, Weimeng Huang, Wenyuan Guo, Hancun Yi, Yirong Yang, Zhuohua Wu, Wei Dai, Hui Sun, Jieyuan Wu, Rui Zhang, Shenqing Zhang, Xiuli Lin, Yuxuan Yong, Xinling Yang, Hongyan Li, Wenjun Wu, Xiaoyun Huang, Zhaoxiang Bian, Hoi Leong Xavier Wong, Xin-Lu Wang, Michael Poppell, Yi Ren, Cong Liu, Wen-Quan Zou, Shengdi Chen, Ping-Yi Xu
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: Translational Neurodegeneration, Vol 13, Iss 1, Pp 1-16 (2024)
Druh dokumentu: article
ISSN: 2047-9158
DOI: 10.1186/s40035-024-00426-9
Popis: Abstract Background Seed amplification assays (SAA) enable the amplification of pathological misfolded proteins, including α-synuclein (αSyn), in both tissue homogenates and body fluids of Parkinson’s disease (PD) patients. SAA involves repeated cycles of shaking or sonication coupled with incubation periods. However, this amplification scheme has limitations in tracking protein propagation due to repeated fragmentation. Methods We introduced a modified form of SAA, known as Quiescent SAA (QSAA), and evaluated biopsy and autopsy samples from individuals clinically diagnosed with PD and those without synucleinopathies (control group). Brain biopsy samples were obtained from 14 PD patients and 6 controls without synucleinopathies. Additionally, skin samples were collected from 214 PD patients and 208 control subjects. Data were analyzed from April 2019 to May 2023. Results QSAA successfully amplified αSyn aggregates in brain tissue sections from mice inoculated with pre-formed fibrils. In the skin samples from 214 PD cases and 208 non-PD cases, QSAA demonstrated high sensitivity (90.2%) and specificity (91.4%) in differentiating between PD and non-PD cases. Notably, more αSyn aggregates were detected by QSAA compared to immunofluorescence with the pS129-αSyn antibody in consecutive slices of both brain and skin samples. Conclusion We introduced the new QSAA method tailored for in situ amplification of αSyn aggregates in brain and skin samples while maintaining tissue integrity, providing a streamlined approach to diagnosing PD with individual variability. The integration of seeding activities with the location of deposition of αSyn seeds advances our understanding of the mechanism underlying αSyn misfolding in PD.
Databáze: Directory of Open Access Journals
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