Detection of skin -synuclein using RT-QuIC as a diagnostic biomarker for Parkinson's disease in the Chinese population

Background Several studies have indicated that skin holds promise as a potential sample for detecting pathological alpha-Syn and serving as a diagnostic biomarker for alpha-synucleinopathies. Despite reports in Chinese PD patients, comprehensive research on skin alpha-Syn detection using RT-QuIC is lacking. Objective This study aimed to evaluate the diagnostic performance of skin samples using RT-QuIC from PD patients in the Chinese population. Methods Patients with sporadic PD and controls were included according to the British PD Association Brain Bank diagnostic criteria. The seeding activity of misfolded alpha-Syn in these skin samples was detected using the RT-QuIC assay after protein extraction. Biochemical and morphological analyses of RT-QuIC products were conducted by atomic force microscopy, transmission electron microscopy, Congo red staining, and dot blot analysis. Result30 patients clinically diagnosed with PD and 28 controls with non-alpha-synucleinopathies were included in this study. 28 of 30 PD patients demonstrated positive alpha-Syn seeding activity by RT-QuIC assay. In contrast, no alpha-Syn seeding activity was detected in the 28 control samples, with an overall sensitivity and specificity of 93.3% and 100%, respectively (P < 0.001). Biochemical characterization of the RT-QuIC product indicated fibrillary alpha-Syn species in PD-seeded reactions, while control samples failed in the conversion of recombinant alpha-Syn substrate. Conclusion This study applied RT-QuIC technology to identify misfolded alpha-Syn seeding activity in skin samples from Chinese PD patients, demonstrating high specificity and sensitivity. Skin alpha-Syn RT-QuIC is expected to be a reliable approach for the diagnosis of PD.