Tear fluid total α-synuclein as a diagnostic biomarker for Parkinson’s disease: a cross-sectional pilot study using non-stimulated basal tears

Parkinson’s disease (PD) lacks noninvasive tools for detecting underlying α-synuclein pathology at an early stage. We evaluated tear fluid total α-synuclein (α-syn) as a diagnostic biomarker for PD using non-stimulated basal tears collected by capillary siphon. Basal tears were collected by capillary siphon without ocular stimulation from 34 PD patients and 27 age- and sex-matched healthy controls. Total α-syn concentrations were measured using an electrochemiluminescence immunoassay (Meso Scale Discovery). Between-group comparisons used the Mann-Whitney U test. Receiver operating characteristic (ROC) curve analysis assessed diagnostic performance; Spearman’s rank correlation examined associations with clinical severity. Tear total α-syn levels were significantly higher in PD patients than in controls (median [interquartile range], 67.26 [36.24–99.28] vs. 25.78 [18.35–47.10] pg/mL; P < 0.001; Cohen’s d = 0.99). The AUC was 0.781 (95% CI, 0.662–0.900); at a cutoff of 33.55 pg/mL, sensitivity was 88.24% and specificity was 66.67%. Tear α-syn levels were not correlated with UPDRS-III score (ρ = −0.171, P = 0.335), Hoehn-Yahr stage (ρ = 0.050, P = 0.780), or disease duration (ρ = −0.058, P = 0.747), and the results were robust to exclusion of two outliers (AUC 0.767). Tear total α-syn in non-stimulated basal tears showed promising diagnostic performance for PD in a predominantly mid-stage cohort and was not significantly associated with clinical severity measures. Validation in larger, multi-center cohorts including early and drug-naive patients is warranted. Not applicable.