Circulating phosphatidylserine as a plasma biomarker for clinical staging and prognostic prediction in Parkinson's disease: A diagnostic validation study.
Abstract
Background
Circulating phosphatidylserine (cPS) may reflect neuronal injury in Parkinson's disease (PD), yet its diagnostic and prognostic utility remains unvalidated. This study aimed to evaluate cPS as a plasma biomarker for PD staging and outcome prediction.
Methods
In this 24-month prospective cohort (STARD-compliant), 120 PD patients (40 early Hoehn and Yahr scale [H&Y] I-II, 40 moderate III, 40 advanced IV-V) and 40 matched controls were enrolled. cPS was quantified via ELISA. Disease severity was assessed by MDS-UPDRS-III and H&Y staging; outcomes included Barthel Index (BI≤40 defining poor prognosis) and cognitive decline (≥4-point Montreal Cognitive Assessment [MoCA] drop). Statistical analyses involved Spearman correlations, ROC curves, mixed-effects models, and multivariable regressions.
Results
Baseline cPS increased with PD severity (control: 35.2 ± 8.45 vs. advanced: 89.45 ± 15.20 ng/mL, P < 0.001), correlating strongly with H&Y stage (ρ = 0.862, P < 0.001), MDS-UPDRS-III (ρ = 0.793, P < 0.001), and BI decline (ρ = -0.817, P < 0.001). ROC analysis showed cPS differentiated advanced vs. early PD with the highest AUC (0.95, 95% CI: 0.90-0.99, cutoff = 67.7 ng/mL, sensitivity = 97.0%, specificity = 82.0%). Longitudinal cPS increases were stage-dependent (early: +6.10 ± 2.45, moderate: +10.30 ± 3.15, advanced: +14.25 ± 4.50 ng/mL/year, P < 0.001). Multivariate Cox regression identified baseline cPS as an independent predictor of 24-month functional decline (BI ≤40: adjusted HR = 1.620, 95% CI: 1.382-1.898, P < 0.001). Logistic regression showed cPS predicted cognitive decline (MoCA ≥4-point drop: adjusted OR = 1.485, P < 0.001), independent of age and education.
Conclusions
cPS levels correlate with PD severity, predict functional and cognitive decline, and exhibit stage-specific longitudinal changes, supporting cPS as a candidate biomarker for PD monitoring, though further validation is required.