Feasibility and safety of multicenter tissue and biofluid sampling for μ -Synuclein in Parkinson's disease: The systemic synuclein sampling study (S4)

Lana M. Chahine, Thomas G. Beach, Nicholas Seedorff, Chelsea Caspell-Garcia, Christopher S. Coffey, Michael Brumm, Charles H. Adler, Geidy E. Serrano, Carly Linder, Sherri Mosovsky, Tatiana Foroud, Holly Riss, Dixie Ecklund, John Seibyl, Danna Jennings, Vanessa Arnedo, Lindsey Riley, K. D. Dave, Brit Mollenhauer

Research output: Contribution to journalArticle

5 Scopus citations

Abstract

Background: μ-synuclein is a lead Parkinson's disease (PD) biomarker. There are conflicting reports regarding accuracy of μ-synuclein in different tissues and biofluids as a PD biomarker, and the within-subject anatomical distribution of μ-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 μ-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 μ-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 μ-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 μ-synuclein is feasible and generally safe. S4 will inform understanding of the concurrent distribution of μ-synuclein pathology and biomarkers in biofluids and peripheral nervous system in PD.

Original languageEnglish (US)
Pages (from-to)517-527
Number of pages11
JournalJournal of Parkinson's disease
Volume8
Issue number4
DOIs
StatePublished - 2018

Keywords

  • Biomarkers
  • Parkinson's disease
  • needle biopsy
  • synucleins

ASJC Scopus subject areas

  • Clinical Neurology
  • Cellular and Molecular Neuroscience

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    Chahine, L. M., Beach, T. G., Seedorff, N., Caspell-Garcia, C., Coffey, C. S., Brumm, M., Adler, C. H., Serrano, G. E., Linder, C., Mosovsky, S., Foroud, T., Riss, H., Ecklund, D., Seibyl, J., Jennings, D., Arnedo, V., Riley, L., Dave, K. D., & Mollenhauer, B. (2018). Feasibility and safety of multicenter tissue and biofluid sampling for μ -Synuclein in Parkinson's disease: The systemic synuclein sampling study (S4). Journal of Parkinson's disease, 8(4), 517-527. https://doi.org/10.3233/JPD-181434