iTRAQ‐based proteomic analysis reveals myeloperoxidase (MPO) as a diagnostic and prognostic biomarker of cognitive decline in Parkinson’s disease
Yi Jayne Tan, Ebonne YL Ng, Samuel YE Ng, Nicole SY Chia, Xinyi Choi, Dede Heng, Shermyn XM Neo, Zheyu Xu, Kay Yaw Tay, Wing Lok Au, Louis CS Tan, Eng‐King Tan, Adeline Su Lyn Ng- Psychiatry and Mental health
- Cellular and Molecular Neuroscience
- Geriatrics and Gerontology
- Neurology (clinical)
- Developmental Neuroscience
- Health Policy
- Epidemiology
Abstract
Background
Parkinson’s disease (PD) is the second most common progressive neurodegenerative disorder and is characterized by loss of dopaminergic neurons, leading to debilitating motor, cognitive, and behavioral symptoms. At present, there are no biological markers for antemortem PD diagnosis.
Methods
To identify potential blood biomarkers of PD, Isobaric Tags for Relative and Absolute Quantitation (iTRAQ)‐based mass spectrometry (MS) was performed to characterize alterations of serum proteins amongst PD patients of varying disease severity according to their Hoehn and Yahr (HY) stages. Sera of mild PD (HY 1.5‐2.0, n = 10), severe PD (HY 3.0‐4.0, n = 10) patients and healthy controls (n = 10) were enriched and subjected to 2D LC‐MS/MS for proteomic analysis. Candidate protein biomarkers were identified based on the relative abundance of the identified tryptic peptides, and were validated using ELISA in a validation set consisting of 103 early PD and 48 healthy controls (HC). Association with clinical outcomes were analyzed at cross‐sectional and longitudinal timepoints.
Results
A total of 96 proteins in the mild PD group and 78 proteins in the severe PD group were found to differ significantly between PD patients and healthy controls. Thirteen proteins were common between the mild PD and severe PD groups and were chosen for further analysis. These dysregulated proteins represent a diversity of biological processes, including innate immune response, complement activation, cytoskeleton reorganization and response to oxidative stress. Of which, myeloperoxidase showed higher serum levels in mild and severe PD. In the validation PD cohort, higher MPO was significantly associated with worse executive function over 4 years.
Conclusion
Using an unbiased proteomic approach, we identified serum MPO (a marker of oxidative stress) as a promising biomarker for PD. Our results suggest that MPO could also potentially be an early marker for cognitive decline in PD. Further studies with larger cohorts are needed to validate these findings.