期刊
EMBO MOLECULAR MEDICINE
卷 13, 期 3, 页码 -出版社
WILEY
DOI: 10.15252/emmm.202013257
关键词
biomarker; DIA; mass spectrometry; Parkinson's disease; urinary proteome
资金
- Michael J. Fox Foundation
- Max Planck Society for the Advancement of Science
- MJFF
- Projekt DEAL
The article presents a mass spectrometry-based proteomic workflow for urinary proteome profiling as a valuable strategy for biomarker discovery and patient stratification in Parkinson's disease (PD). The study found significant differences in urinary proteome between PD patients and healthy controls, as well as between LRRK2 G2019S carriers and non-carriers, with lysosomal dysregulation in LRRK2 G2019S mutation carriers. When combined with machine learning, the urinary proteome data alone could effectively classify mutation status and disease manifestation in PD patients.
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.
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