Objective: To identify novel Parkinson’s disease (PD) blood biomarkers using unbiased shotgun mass spectrometry.

Background: PD is a common neurodegenerative disorder diagnosed based on its cardinal motor features. Accurate, specific, and reproducible fluid biomarkers for PD are currently lacking. However, major progress has recently been made, not least with the development of seeding aggregation assays (SAA) and quantification of DOPA decarboxylase in cerebrospinal fluid (CSF). Early and accurate diagnosis of PD is crucial for future implementation of disease-modifying therapies. Modern proteomic techniques have enabled high-throughput analyses. Mass spectrometry provides an unbiased approach to identifying novel biomarkers, and the plasma proteome reflects ongoing disease processes throughout the body, including the central nervous system. Blood plasma is more accessible than CSF in routine clinical practice and has proven useful for accurate quantification of biomarkers in other neurodegenerative diseases.

Method: Plasma from 198 individuals (130 PD and 68 controls) from the Swedish Biopark cohort were TMT-tagged, pre-fractionated, and analysed using untargeted mass spectrometry. Robust peptides from candidate biomarkers were validated using parallel reaction monitoring (PRM). Data were primarily analysed to identify diagnostic PD biomarkers and secondarily to identify biomarkers reflecting both motor and non-motor symptoms.

Results: Several promising candidate biomarkers were discovered for PD diagnosis, cognitive decline, and motor impairment in the discovery phase. Additionally, an overall difference in the plasma proteome was identified in PD, with complement and coagulation pathways being the most implicated. Peptides from six of the 12 proteins quantified with PRM correlated with quantifications from the discovery phase. Following PRM validation, it was found that peptides from C9 and APOC3 had altered levels in PD compared with controls. Additionally SAA1 was found to be associated with both cognitive and motor impairment.

Conclusion: In conclusion, mass spectrometry proved to be a viable method for generating novel candidate biomarkers in PD plasma in our study, several of which were validated using a targeted PRM approach, including SAA1, C9, and APOC3.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/large-scale-shotgun-mass-spectrometry-in-parkinsons-disease-plasma-identifies-novel-biomarker-candidates/