Urinary proteome profiling for stratifying patients with familial Parkinson’s disease
Open Access
- 22 January 2021
- journal article
- research article
- Published by Springer Science and Business Media LLC in EMBO Molecular Medicine
- Vol. 13 (3), e13257
- https://doi.org/10.15252/emmm.202013257
Abstract
The prevalence of Parkinson's disease (PD) is increasing but the development of novel treatment strategies and therapeutics altering the course of the disease would benefit from specific, sensitive, and non‐invasive biomarkers to detect PD early. Here, we describe a scalable and sensitive mass spectrometry (MS)‐based proteomic workflow for urinary proteome profiling. Our workflow enabled the reproducible quantification of more than 2,000 proteins in more than 200 urine samples using minimal volumes from two independent patient cohorts. The urinary proteome was significantly different between PD patients and healthy controls, as well as between LRRK2 G2019S carriers and non‐carriers in both cohorts. Interestingly, our data revealed lysosomal dysregulation in individuals with the LRRK2 G2019S mutation. When combined with machine learning, the urinary proteome data alone were sufficient to classify mutation status and disease manifestation in mutation carriers remarkably well, identifying VGF, ENPEP, and other PD‐associated proteins as the most discriminating features. Taken together, our results validate urinary proteomics as a valuable strategy for biomarker discovery and patient stratification in PD.Funding Information
- Michael J. Fox Foundation for Parkinson's Research (6986)
This publication has 97 references indexed in Scilit:
- Plasma apolipoprotein A1 as a biomarker for Parkinson diseaseAnnals of Neurology, 2013
- Urine proteomics for discovery of improved diagnostic markers of Kawasaki diseaseEMBO Molecular Medicine, 2012
- Targeted Data Extraction of the MS/MS Spectra Generated by Data-independent Acquisition: A New Concept for Consistent and Accurate Proteome AnalysisMolecular & Cellular Proteomics, 2012
- Disruption of Protein Quality Control in Parkinson's DiseaseCold Spring Harbor Perspectives in Medicine, 2012
- Multi-organ autonomic dysfunction in Parkinson diseaseParkinsonism & Related Disorders, 2011
- Distribution of VGF peptides in the human cortex and their selective changes in Parkinson’s and Alzheimer’s diseasesJournal of Anatomy, 2010
- Urine proteomics for profiling of human disease using high accuracy mass spectrometryProteomics – Clinical Applications, 2009
- Proteomic profiling of urine for the detection of colon cancerProteome Science, 2008
- Urinary Proteomic Biomarkers in Coronary Artery DiseaseMolecular & Cellular Proteomics, 2008
- Dynamic and redundant regulation of LRRK2 and LRRK1 expressionBMC Neuroscience, 2007