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Proteomics Clin Appl. 2017 Jul;11(7-8). doi: 10.1002/prca.201700045. Epub 2017 Apr 19.

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

Author information

1
Department of Pathology, University of Washington, Seattle, WA, USA.
2
Department of Pathology, No. 3 Hospital of Beijing University, Beijing, China.
3
Pacific Northwest National Laboratory, Richland, WA, USA.
4
Parkinson's Disease Research and Geriatric Research, Education and Clinical Center, Veterans Affairs Puget Sound Health Care System, Seattle, WA, USA.
5
Department of Neurology, University of Washington School of Medicine, Seattle, WA, USA.
6
Department of Neurology, Oregon Health and Science University, Portland, OR, USA.
7
Department of Pathology, Peking University Health Science Centre and Third Hospital, Beijing, 100083, China.

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.

KEYWORDS:

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

PMID:
28319654
PMCID:
PMC5540649
DOI:
10.1002/prca.201700045
[Indexed for MEDLINE]
Free PMC Article

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