Objective: To identify reliable diagnostic and prognostic protein biomarkers for early-stage Parkinson’s disease (PD) using large-scale proteomic profiling of plasma and cerebrospinal fluid (CSF).To identify reliable diagnostic and prognostic protein biomarkers for early-stage Parkinson’s disease (PD) using large-scale proteomic profiling of plasma and cerebrospinal fluid (CSF).

Background: PD is a common neurodegenerative disorder with no disease-modifying therapy. Reliable biomarkers for early diagnosis and prognosis are urgently needed. Proteomics offers a powerful approach to discover such biomarkers in accessible body fluids.

Method: We performed unbiased, large-scale, ultra-deep mass spectrometry-based proteomics on plasma and CSF samples from early-stage PD patients (Hoehn & Yahr 1–2, disease duration ≤2 years) and healthy controls (HCs). The discovery cohort included 181 PD and 521 HC plasma samples, and 24 PD and 31 HC CSF samples. Differential expression analysis, machine learning-based feature selection, and receiver operating characteristic (ROC) analysis were used to identify diagnostic biomarkers. Longitudinal analysis of plasma proteins was conducted to identify markers associated with motor progression.

Results: We quantified 11,847 plasma and 2,585 CSF proteins. In early PD, 677 plasma and 57 CSF proteins were differentially expressed. A panel of five plasma proteins (HSPD1, ACTBL2, SERPING1, MX1, and CNOT3) demonstrated high diagnostic accuracy (AUC = 0.965 in discovery, AUC = 1.000 and 0.901 in two independent validation cohorts). In CSF, ASAH1 best discriminated PD from HCs (AUC = 1.000). Longitudinal analysis identified six plasma proteins (INA, PLXNB2, RDX, UQCC1, HSD17B4, and EIFA41) whose expression trends correlated with disease stage and motor progression. Baseline levels of INA and ORM1 were associated with motor severity scores.

Conclusion: We identified a five-plasma-protein panel and a CSF protein (ASAH1) as promising diagnostic biomarkers for early PD. Six longitudinal plasma proteins may serve as prognostic markers for disease progression. These findings provide a foundation for developing clinically useful biomarkers for early diagnosis and prediction of PD.

Overview of the study design

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MDS Abstracts - https://www.mdsabstracts.org/abstract/parkinsons-disease-early-diagnostic-and-prognostic-biomarkers-identified-by-large-scale-plasma-and-cerebrospinal-fluid-proteomic-profiling/