Objective: Investigating proteomic changes preceding MSA onset to provide critical insights into disease biology, uncover novel biomarkers for early detection, and identify potential therapeutic targets.

Background: Emerging evidence suggests that alterations in plasma protein levels may occur in individuals at risk for multiple system atrophy (MSA), potentially reflecting early disease processes.

Method: Using data from the UK Biobank, we examined the association between baseline levels of 2,923 plasma protein analytes and the risk of developing MSA. Cox proportional hazards regression analysis was employed to assess the relationships. Additionally, protein-wide Mendelian randomization (MR) was conducted using summary statistics from large protein quantitative trait locus (pQTL) datasets to identify proteins causally linked to MSA risk.

Results: Three proteins (GGA1, SCP2, and RABEPK) were significantly associated with an increased risk of MSA. Notably, GGA1 remained significantly associated with MSA even when compared to individuals with Parkinson’s disease as controls. Causation inference analysis identified APCS and IGFBP1 as proteins causally linked to increased risk of MSA. Pathway enrichment analysis implicated growth factor binding in MSA pathogenesis.

Conclusion: This study enhances our understanding of MSA pathogenesis through a proteomic lens. The identified proteins hold promise as non-invasive biomarkers for MSA, offering potential avenues for diagnostic and therapeutic advancements.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/proteomic-analysis-identifies-gga1-scp2-and-rabepk-as-risk-protein-of-multiple-system-atrophy/