Aim: The alpha-synuclein (a-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 a-syn are inconsistent among studies with large cohorts and different measurement platforms. Total a-syn level also does not correlate with disease severity or progression. Here, we developed a highly sensitive Multiple Reaction Monitoring (MRM) method to measure absolute CSF a-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 a-syn in human CSF was determined to be 2.1ng/mL. A unique a-syn peptide, TVEGAGSIAAATGFVK (81-96), displayed excellent correlation with previous immunoassay results in two independent PD cohorts (p
Revised: August 28, 2017 |
Published: April 19, 2017
Citation
Yang L., T. Stewart, M. Shi, G. Pottiez, R. Dator, R. Wu, and P. Aro, et al. 2017.An alpha-synuclein MRM assay with diagnostic potential for Parkinson’s disease and monitoring disease progression.Proteomics - Clinical Applications 11, no. 7-8:Article No. 1700045.PNNL-SA-124743.doi:10.1002/prca.201700045