Premium
An alpha‐synuclein MRM assay with diagnostic potential for Parkinson's disease and monitoring disease progression
Author(s) -
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 ShuChing,
Quinn Joseph F.,
Zhang Jing
Publication year - 2017
Publication title -
proteomics – clinical applications
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.948
H-Index - 54
eISSN - 1862-8354
pISSN - 1862-8346
DOI - 10.1002/prca.201700045
Subject(s) - biomarker , disease , immunoassay , parkinson's disease , medicine , cerebrospinal fluid , oncology , immunology , biology , antibody , genetics
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.