Objective: We aimed to identify distinct plasma proteins in patients with Parkinson’s disease (PD) and multiple system atrophy (MSA) and evaluate their associations with disease severity and diagnostic potential.
Background: Both PD and MSA are neurodegenerative disorders characterized by progressive neuronal degeneration and abnormal alpha-synuclein aggregation. Growing evidence suggests that alterations in plasma protein profiles may reflect underlying disease mechanisms and serve as potential biomarkers for diagnosis and disease progression. Understanding protein dysregulation in PD and MSA could provide valuable insights into distinct pathogenic pathways and aid in differentiating these disorders.
Method: Plasma proteins from 69 patients with PD, 38 patients with MSA, and 69 healthy controls (HC) were profiled using Olink multiplex immunoassay (92 proteins related to neurological disorders and 92 proteins related to inflammation). Statistical analyses included age-adjusted ANCOVA, pathway analysis, and logistic regression to identify key proteins distinguishing PD from MSA.
Results: In multiplex protein immunoassay, 31 proteins were elevated in both PD and MSA compared to HC, with 7 proteins significantly differentiating PD from MSA, including NEFL and PRTFDC1. Combined NEFL and PRTFDC1 achieved an AUC of 0.92 when discriminating PD and MSA. In patients with PD, most elevated proteins showed a negative correlation with disease duration, indicating early-stage specificity. Pathway analysis highlighted mTOR and AMPK signaling in both diseases, with HMOX2-linked heme degradation enriched in PD and AXIN1-associated WNT/β-catenin signaling enriched in MSA.
Conclusion: This study revealed that dysregulation of mTOR and AMPK signaling pathways plays a critical role in both PD and MSA, assessed by multiplex plasma protein immunoassay. Moreover, the enrichment of HMOX2-linked heme degradation in PD and AXIN1-associated WNT/β-catenin signaling in MSA highlights distinct and disease-specific pathogenic mechanisms.
To cite this abstract in AMA style:
SJ. Chung, S. Jo, I. Jang, J. Lee, M. Choi, E. Lee. Plasma Protein Profiles Reveal Distinct Molecular Signatures in Parkinson’s Disease and Multiple System Atrophy [abstract]. Mov Disord. 2025; 40 (suppl 1). https://www.mdsabstracts.org/abstract/plasma-protein-profiles-reveal-distinct-molecular-signatures-in-parkinsons-disease-and-multiple-system-atrophy/. Accessed October 13, 2026.« Back to 2025 International Congress
MDS Abstracts - https://www.mdsabstracts.org/abstract/plasma-protein-profiles-reveal-distinct-molecular-signatures-in-parkinsons-disease-and-multiple-system-atrophy/