Plasma TNF-α and phosphorylated α-syn are associated with fatigue in patients with Parkinson's disease.

Backgroud: Fatigue is one of the most common non-motor symptoms among patients with Parkinson's disease (PD).However, the pathogenesis keeps largely unknown. Moreover, it is lack of objective biomarker.

Objective: To investigate the relationship between plasma inflammatory cytokines and α-syn levels and fatigue in patients with PD.

Methods: A total of 63 PD patients were enrolled, including 35 patients with fatigue and 28 patients without fatigue. We compared the difference between plasma cytokines and alpha-synuclein (α-syn) in the two groups. Meanwhile, we analyzed the relationship between plasma cytokines and p-α-syn levels and fatigue.

Results: PD patients with fatigue had older age, longer disease duration, more severe motor scores. There were significant differences in the plasma levels of IL-1β, IL-18, TNF-α, and phosphorylated α-syn (p-α-syn) between the two groups. The plasm inflammatory cytokine levels (IL-1β, IL-18 and TNF-α) were positively associated with FSS scores. Moreover, the plasma p-α-syn level was significantly positively correlated with FSS scores. Furthermore, the higher PDQ-39 scores and higher plasma levels of TNF-α and p-α-syn were strongly associated with fatigue in PD. The ROC curve analysis showed the AUC of TNF-α for fatigue in PD was 0.663 with a sensitivity of 65.71% and specificity of 67.86%, while the AUC of p-α-syn was 0.786 with a sensitivity of 74.29% and specificity of 64.29%. The combination of TNF-α and p-α-syn improves the AUC to 0.803 with a sensitivity of 88.57% and specificity of 64.29%.

Conclusion: The high plasma levels of TNF-α and p-α-syn were strongly associated with fatigue in PD.