Feasibility and Safety of Multicenter Tissue and Biofluid Sampling for alpha-Synuclein in Parkinson's Disease: The Systemic Synuclein Sampling Study (S4)

Background: alpha-synuclein is a lead Parkinson's disease (PD) biomarker. There are conflicting reports regarding accuracy of alpha-synuclein in different tissues and biofluids as a PD biomarker, and the within-subject anatomical distribution of alpha-synuclein is not well described. The Systemic Synuclein Sampling Study (S4) aims to address these gaps in knowledge. The S4 is a multicenter, cross-sectional, observational study evaluating alpha-synuclein in multiple tissues and biofluids in PD and healthy controls (HC). Objective: To describe the baseline characteristics of the S4 cohort and safety and feasibility of this study. Methods: Participants underwent motor and non-motor clinical assessments, dopamine transporter SPECT, biofluid collection (cerebrospinal fluid, saliva, and blood), and tissue biopsies (skin, sigmoid colon, and submandibular gland). Biopsy adequacy was determined based on presence of adequate target tissue. Tissue sections were stained with the 5C12 monoclonal antibody against unmodified alpha-synuclein. All specimens were acquired and processed in a standardized manner. Adverse events were systematically recorded. Results: The final cohort consists of 82 participants (61 PD, 21 HC). In 68 subjects (83%), all types of specimens were obtained but only 50 (61%) of subjects had all specimens both collected and evaluable for alpha-synuclein. Mild adverse events were common, especially for submandibular gland biopsy, but only 1 severe adverse event occurred. Conclusion: Multicenter tissue and biofluid sampling for alpha-synuclein is feasible and generally safe. S4 will inform understanding of the concurrent distribution of alpha-synuclein pathology and biomarkers in biofluids and peripheral nervous system in PD.