Collaborative plasma biomarkers for Parkinson disease development and progression: A cross-sectional and longitudinal study.

Background And Purpose: Relying on a single biomarker for early diagnosis of Parkinson disease (PD) may not yield accurate results. We aimed to assess the combined diagnostic value of multiple biomarkers, including plasma CCL2, plasma CXCL12, and plasma neuronal exosomal α-synuclein (α-syn) for early stage PD diagnosis and their predictive value in PD progression.

Methods: This study included both cross-sectional and longitudinal designs. The CCL2, CXCL12, and neuronal exosomal α-syn levels were analyzed in 50 healthy controls (HCs) and 50 early stage PD patients. Then, a prospective follow-up of 30 early stage PD patients was performed.

Results: In early stage PD, we observed a significant increase in CCL2, CXCL12, and plasma neuronal exosomal α-syn compared to HCs (p < 0.05). Utilizing a combined diagnostic approach of CCL2, CXCL12, and α-syn significantly improved the area under the curve (AUC = 0.89, p < 0.001). Spearman correlation analysis revealed that CCL2 levels were correlated with PD clinical stage and autonomic symptoms (p < 0.05). CXCL12 levels were associated with nonmotor symptoms (p < 0.05). Plasma neuronal exosomal α-syn levels were connected to the clinical stage, motor symptoms, and nonmotor symptoms in early stage PD (p < 0.01). In the longitudinal cohort, the Cox regression analysis showed that high CCL2 levels were associated with motor progression after a mean follow-up of 24 months.

Conclusions: Our study suggested that the combined measurement of plasma CCL2, CXCL12, and neuronal exosomal α-syn can improve early stage PD diagnosis, and CCL2 may serve as a prognostic marker for PD progression.