Baseline and follow-up synaptic protein levels in plasma extracellular vesicles (EVs) between patients with Parkinson’s disease (PwP) and healthy controls (HCs). (A) Representative protein blot images of different synaptic proteins, including SNAP-25, GAP-43, and synaptotagmin-1. Heat shock protein 70 (HSP-70) was the protein loading control. (B–D) Comparison of plasma SNAP-25, GAP-43, and synaptotagmin-1 levels between PwP and HCs at baseline and follow-up. Data are presented using a dot plot displaying the median and first and third quartile values. n.s., non-significant.

Demographic data of study participants

Generalized linear model investigated the association between the change of plasma EV synaptic proteins (per 100%) with the change of clinical severity as dependent variable in people with Parkinson’s disease, presented as coefficient with p value. n.s., non-significant

Heatmap of the association between baseline plasma extracellular vesicle (EV) synaptic protein levels and clinical assessment parameters at follow-up in patients with Parkinson’s disease (PwP). The logistic regression model was used to assess the baseline plasma EV SNAP-25, GAP-43, and synaptotagmin-1 levels. The motor symptoms were assessed based on the Unified Parkinson Disease Rating Scale (UPDRS)-II and UPDRS-III scores and tremor, akinetic rigidity (AR), and postural instability and gait disturbance (PIGD) subscores, and cognitive function was assessed using the Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) scores. The association is presented using standardized β values. Detailed results of the regression model are provided in Supplementary Table. *, p < 0.05; **, p < 0.01.

The clinical severity in people with Parkinson’s disease with and without elevated (1st quartile) baseline plasma extracellular vesicle (EV) synaptosome-associated protein 25 (SNAP-25), growth-associated protein 43 (GAP-43) and synaptotagmin-1.

Changes in estimated marginal means of Unified Parkinson Disease Rating Scale (UPDRS)-II total scores (A) and postural instability and gait disturbance (PIGD) subscores (B) after adjustment for age, sex, and disease duration in patients with Parkinson’s disease (PwP) with and without elevated levels of any one plasma extracellular vesicle synaptic protein (first quartile) at baseline and follow-up. Data are presented as means with 95% confidence intervals. n.s., nonsignificant.