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Longitudinal blood-based proteomics reveal progression-specific molecular signatures in Parkinson’s disease

Year: 2026

Type: article

Abstract: Parkinson disease (PD) shows marked heterogeneity in clinical progression and single baseline biomarkers have shown limited value for predicting these changes. We examined whether repeated serum proteomics can identify protein-clinical associations linked to worsening across motor, cognitive, non-motor, and treatment-related outcomes. We analysed 166 patients with PD from the prospective PROMOVE registry with repeated OFF-state clinical assessments and longitudinal serum proteomics covering 297 proteins. For each outcome, participants were classified as worsening or non-worsening based on individual longitudinal slopes. In worsening participants, all proteins were tested using linear mixed-effects models that separated within- from between-subject protein effects. Six associations remained significant after FDR correction. Higher DDC was associated with increasing levodopa equivalent daily dose. Higher CD276 and POSTN were associated with worse MDS-UPDRS II scores, while higher VEGF-C and IL19 were associated with worse MDS-UPDRS III scores. Higher IL12 was associated with lower MMSE scores. The five non-treatment associations remained significant after additional adjustment for time-varying dopaminergic treatment. Repeated serum proteomics identified distinct protein-clinical associations in patients showing clinical worsening. The findings point to treatment-related, immune, vascular, and extracellular-matrix processes and suggest that longitudinal proteomics may complement clinical measures when monitoring PD progression.

Source: npj Parkinson s Disease

DOI: 10.1038/s41531-026-01608-0