An alpha-synuclein MRM assay with diagnostic potential for Parkinson's disease and monitoring disease progression

Li Yang, Tessandra Stewart, Min Shi, Gwenael Pottiez, Romel Dator, Rui Wu, Patrick Aro, Robert J. Schuster, Carmen Ginghina, Catherine Pan, Yuqian Gao, Weijun Qian, Cyrus P. Zabetian, Shu Ching Hu, Joseph Quinn, Jing Zhang

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Aim: The alpha-synuclein (α-syn) level in human cerebrospinal fluid (CSF), as measured by immunoassays, is promising as a Parkinson's disease (PD) biomarker. However, the levels of total α-syn are inconsistent among studies with large cohorts and different measurement platforms. Total α-syn level also does not correlate with disease severity or progression. Here, the authors developed a highly sensitive MRM method to measure absolute CSF α-syn peptide concentrations without prior enrichment or fractionation, aiming to discover new candidate biomarkers. Results: Six peptides covering 73% of protein sequence were reliably identified, and two were consistently quantified in cross-sectional and longitudinal cohorts. Absolute concentration of α-syn in human CSF was determined to be 2.1 ng/mL. A unique α-syn peptide, TVEGAGSIAAATGFVK (81-96), displayed excellent correlation with previous immunoassay results in two independent PD cohorts (p < 0.001), correlated with disease severity, and its changes significantly tracked the disease progression longitudinally. Conclusions: An MRM assay to quantify human CSF α-syn was developed and optimized. Sixty clinical samples from cross-sectional and longitudinal PD cohorts were analyzed with this approach. Although further larger scale validation is needed, the results suggest that α-syn peptide could serve as a promising biomarker in PD diagnosis and progression.

Original languageEnglish (US)
Article number1700045
JournalProteomics - Clinical Applications
Volume11
Issue number7-8
DOIs
StatePublished - Jul 1 2017

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alpha-Synuclein
Parkinson Disease
Cerebrospinal Fluid
Disease Progression
Assays
Cerebrospinal fluid
Peptides
Monitoring
Biomarkers
Immunoassay
Fractionation
Proteins

Keywords

  • alpha-synuclein (α-syn)
  • Diagnosis
  • MRM
  • Parkinson's disease
  • Progression

ASJC Scopus subject areas

  • Clinical Biochemistry

Cite this

An alpha-synuclein MRM assay with diagnostic potential for Parkinson's disease and monitoring disease progression. / Yang, Li; Stewart, Tessandra; Shi, Min; Pottiez, Gwenael; Dator, Romel; Wu, Rui; Aro, Patrick; Schuster, Robert J.; Ginghina, Carmen; Pan, Catherine; Gao, Yuqian; Qian, Weijun; Zabetian, Cyrus P.; Hu, Shu Ching; Quinn, Joseph; Zhang, Jing.

In: Proteomics - Clinical Applications, Vol. 11, No. 7-8, 1700045, 01.07.2017.

Research output: Contribution to journalArticle

Yang, L, Stewart, T, Shi, M, Pottiez, G, Dator, R, Wu, R, Aro, P, Schuster, RJ, Ginghina, C, Pan, C, Gao, Y, Qian, W, Zabetian, CP, Hu, SC, Quinn, J & Zhang, J 2017, 'An alpha-synuclein MRM assay with diagnostic potential for Parkinson's disease and monitoring disease progression', Proteomics - Clinical Applications, vol. 11, no. 7-8, 1700045. https://doi.org/10.1002/prca.201700045
Yang, Li ; Stewart, Tessandra ; Shi, Min ; Pottiez, Gwenael ; Dator, Romel ; Wu, Rui ; Aro, Patrick ; Schuster, Robert J. ; Ginghina, Carmen ; Pan, Catherine ; Gao, Yuqian ; Qian, Weijun ; Zabetian, Cyrus P. ; Hu, Shu Ching ; Quinn, Joseph ; Zhang, Jing. / An alpha-synuclein MRM assay with diagnostic potential for Parkinson's disease and monitoring disease progression. In: Proteomics - Clinical Applications. 2017 ; Vol. 11, No. 7-8.
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AU - Yang, Li

AU - Stewart, Tessandra

AU - Shi, Min

AU - Pottiez, Gwenael

AU - Dator, Romel

AU - Wu, Rui

AU - Aro, Patrick

AU - Schuster, Robert J.

AU - Ginghina, Carmen

AU - Pan, Catherine

AU - Gao, Yuqian

AU - Qian, Weijun

AU - Zabetian, Cyrus P.

AU - Hu, Shu Ching

AU - Quinn, Joseph

AU - Zhang, Jing

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Y1 - 2017/7/1

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AB - Aim: The alpha-synuclein (α-syn) level in human cerebrospinal fluid (CSF), as measured by immunoassays, is promising as a Parkinson's disease (PD) biomarker. However, the levels of total α-syn are inconsistent among studies with large cohorts and different measurement platforms. Total α-syn level also does not correlate with disease severity or progression. Here, the authors developed a highly sensitive MRM method to measure absolute CSF α-syn peptide concentrations without prior enrichment or fractionation, aiming to discover new candidate biomarkers. Results: Six peptides covering 73% of protein sequence were reliably identified, and two were consistently quantified in cross-sectional and longitudinal cohorts. Absolute concentration of α-syn in human CSF was determined to be 2.1 ng/mL. A unique α-syn peptide, TVEGAGSIAAATGFVK (81-96), displayed excellent correlation with previous immunoassay results in two independent PD cohorts (p < 0.001), correlated with disease severity, and its changes significantly tracked the disease progression longitudinally. Conclusions: An MRM assay to quantify human CSF α-syn was developed and optimized. Sixty clinical samples from cross-sectional and longitudinal PD cohorts were analyzed with this approach. Although further larger scale validation is needed, the results suggest that α-syn peptide could serve as a promising biomarker in PD diagnosis and progression.

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