Objective: To identify proteins associated with risk of Parkinson’s disease (PD).

Background: Alterations in plasma protein levels manifest early in individuals at risk of PD. Unveiling proteomic changes preceding PD holds the potential to unravel disease biology and shed light on prospective biomarkers for intervention avenues.

Method: Utilizing data from the UK Biobank, we delved into the association between baseline levels of 2,923 protein analytes and the risk of incident PD, employing Cox proportional hazards regression analysis. As a replication step, we explored the connection between the identified proteins and risk of PD in an independent cohort from AMP-PD. Protein-wide Mendelian randomization analysis was conducted to identify causative proteins of PD. We further evaluated whether the identified proteins could aid in predicting PD incidence.

Results: A total of 14 proteins exhibited significant association with the risk of PD in the discovery stage. In the replication cohort, association was observed for 11 proteins with the same effect direction. Causal inference analysis highlighted the proteins PM20D1 and PRSS53 were linked to a reduced risk of PD. Pathway enrichment analysis implicated dopamine metabolic process, amine metabolism, neutrophil activation, and cell adhesion in the pathogenesis of PD. The integration of plasma proteomic profiles with clinical characteristics significantly enhanced the accuracy of predicting PD incidence.

Conclusion: This study enriches our comprehension of PD pathogenesis from a proteomic perspective. The identified proteins emerge as potential non-invasive biomarkers for PD, opening promising avenues for diagnostic and therapeutic advancements.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/plasma-proteomic-pro%ef%ac%81les-and-risk-of-parkinsons-disease-a-prospective-study-from-uk-biobank/