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

Systemic sSynuclein Sampling study

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

BACKGROUND: α-synuclein is a lead Parkinson's disease (PD) biomarker. There are conflicting reports regarding accuracy of α-synuclein in different tissues and biofluids as a PD biomarker, and the within-subject anatomical distribution of α-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 α-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 α-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 α-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 α-synuclein is feasible and generally safe. S4 will inform understanding of the concurrent distribution of α-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 - Jan 1 2018

Fingerprint

Synucleins
Sampling Studies
Parkinson Disease
Safety
Submandibular Gland
Biomarkers
Biopsy
Dopamine Plasma Membrane Transport Proteins
Peripheral Nervous System
Feasibility Studies
Sigmoid Colon
Single-Photon Emission-Computed Tomography
Saliva
Observational Studies
Cerebrospinal Fluid
Cross-Sectional Studies
Monoclonal Antibodies
Pathology

Keywords

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

ASJC Scopus subject areas

  • Clinical Neurology
  • Cellular and Molecular Neuroscience

Cite this

Feasibility and Safety of Multicenter Tissue and Biofluid Sampling for α-Synuclein in Parkinson's Disease : The Systemic Synuclein Sampling Study (S4). / Systemic sSynuclein Sampling study.

In: Journal of Parkinson's Disease, Vol. 8, No. 4, 01.01.2018, p. 517-527.

Research output: Contribution to journalArticle

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title = "Feasibility and Safety of Multicenter Tissue and Biofluid Sampling for α-Synuclein in Parkinson's Disease: The Systemic Synuclein Sampling Study (S4)",
abstract = "BACKGROUND: α-synuclein is a lead Parkinson's disease (PD) biomarker. There are conflicting reports regarding accuracy of α-synuclein in different tissues and biofluids as a PD biomarker, and the within-subject anatomical distribution of α-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 α-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 α-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 α-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 α-synuclein is feasible and generally safe. S4 will inform understanding of the concurrent distribution of α-synuclein pathology and biomarkers in biofluids and peripheral nervous system in PD.",
keywords = "Biomarkers, needle biopsy, Parkinson’s disease, synucleins",
author = "{Systemic sSynuclein Sampling study} and Chahine, {Lana M.} and Beach, {Thomas G.} and Nicholas Seedorff and Chelsea Caspell-Garcia and Coffey, {Christopher S.} and Michael Brumm and Adler, {Charles Howard} and Serrano, {Geidy E.} and Carly Linder and Sherri Mosovsky and Tatiana Foroud and Holly Riss and Dixie Ecklund and John Seibyl and Danna Jennings and Vanessa Arnedo and Lindsey Riley and Dave, {K. D.} and Brit Mollenhauer",
year = "2018",
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T1 - Feasibility and Safety of Multicenter Tissue and Biofluid Sampling for α-Synuclein in Parkinson's Disease

T2 - The Systemic Synuclein Sampling Study (S4)

AU - Systemic sSynuclein Sampling study

AU - Chahine, Lana M.

AU - Beach, Thomas G.

AU - Seedorff, Nicholas

AU - Caspell-Garcia, Chelsea

AU - Coffey, Christopher S.

AU - Brumm, Michael

AU - Adler, Charles Howard

AU - Serrano, Geidy E.

AU - Linder, Carly

AU - Mosovsky, Sherri

AU - Foroud, Tatiana

AU - Riss, Holly

AU - Ecklund, Dixie

AU - Seibyl, John

AU - Jennings, Danna

AU - Arnedo, Vanessa

AU - Riley, Lindsey

AU - Dave, K. D.

AU - Mollenhauer, Brit

PY - 2018/1/1

Y1 - 2018/1/1

N2 - BACKGROUND: α-synuclein is a lead Parkinson's disease (PD) biomarker. There are conflicting reports regarding accuracy of α-synuclein in different tissues and biofluids as a PD biomarker, and the within-subject anatomical distribution of α-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 α-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 α-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 α-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 α-synuclein is feasible and generally safe. S4 will inform understanding of the concurrent distribution of α-synuclein pathology and biomarkers in biofluids and peripheral nervous system in PD.

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

KW - Biomarkers

KW - needle biopsy

KW - Parkinson’s disease

KW - synucleins

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