Proteomics identifies potential biomarkers and implicates the granin family in Parkinson’s disease

ABSTRACT: Parkinson’s disease (PD) is the second most common neurodegenerative disorder. Treatments are available to address PD motor symptoms, but not disease progression or cognitive decline. Demonstrating disease modification in clinical trials is still a substantial challenge because of the high disease heterogeneity and variability in progression as well as subjectivity in clinical scoring. To develop novel therapeutics for PD, there is an urgent need to identify biomarkers for patient stratification in clinical trials. In this study, we used cutting edge data-independent acquisition (DIA) mass spectrometry to identify PD-specific biomarkers in patient cerebrospinal fluid (CSF). To identify novel biomarkers with minimal false discovery, two independent cohorts were analyzed by DIA mass spectrometry. An initial discovery cohort of 53 PD and 72 control (CTRL) patient samples was analyzed, identifying 53 proteins with significant changes (nominal p-value ≤ 0.05) in PD relative to CTRL out of the 342 detectable proteins. A second cohort of 28 PD and 43 CTRL samples were analyzed as above and identified 41 proteins with significant changes in PD. Thirteen proteins showed significant changes in both cohorts, some of which are previously reported to be altered in PD (i.e., EPHA4 and SERPINC1). Three members of a specific protein family, which are cleaved into bioactive peptides, were amongst these 13 proteins . Further, peptide-level quantification of the detectable members of this protein family (7 total) revealed that specific regions of all 7 proteins are decreased in Parkinson’s disease samples. Together, these data may implicate altered processing, localization, and/or function of this entire protein family for the first time in PD.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cerebrospinal Fluid

DISEASE(S): Parkinson's Disease

SUBMITTER: Pablo Sardi  

LAB HEAD: Sergio Pablo Sardi

PROVIDER: PXD011216 | Pride | 2020-02-19

REPOSITORIES: Pride