An alpha-synuclein MRM assay with diagnostic potential for Parkinson's disease and monitoring disease progression.
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ABSTRACT: The alpha-synuclein (?-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 ?-syn are inconsistent among studies with large cohorts and different measurement platforms. Total ?-syn level also does not correlate with disease severity or progression. Here, the authors developed a highly sensitive MRM method to measure absolute CSF ?-syn peptide concentrations without prior enrichment or fractionation, aiming to discover new candidate biomarkers.Six peptides covering 73% of protein sequence were reliably identified, and two were consistently quantified in cross-sectional and longitudinal cohorts. Absolute concentration of ?-syn in human CSF was determined to be 2.1 ng/mL. A unique ?-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.An MRM assay to quantify human CSF ?-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 ?-syn peptide could serve as a promising biomarker in PD diagnosis and progression.
SUBMITTER: Yang L
PROVIDER: S-EPMC5540649 | biostudies-literature | 2017 Jul
REPOSITORIES: biostudies-literature
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