Cytokine Profile in Plasma Extracellular Vesicles of Parkinson's Disease and the Association with Cognitive Function

Abstract

Plasma extracellular vesicles (EVs) containing various molecules, including cytokines, can reflect the intracellular condition and participate in cell-to-cell signaling, thus emerging as biomarkers for Parkinson's disease (PD). Inflammation may be a crucial risk factor for PD development and progression. The present study investigated the role of plasma EV cytokines as the biomarkers of PD. This cross-sectional study recruited 113 patients with PD, with mild to moderate stage disease, and 48 controls. Plasma EVs were isolated, and the levels of cytokines, including pro-interleukin (IL)-1β, IL-6, IL-10, tumor necrosis factor (TNF)-α, and transforming growth factor (TGF)-β1, were evaluated. Patients with PD had significantly increased plasma EV pro-IL-1β and TNF-α levels compared with controls after adjustment for age and sex. Despite the lack of a significant association between plasma EV cytokines and motor symptom severity in patients with PD, cognitive dysfunction severity, assessed using the Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment, was significantly associated with plasma EV pro-IL-1β, IL-6, IL-10, and TNF-α levels. This association was PD specific and not found in controls. Furthermore, patients with PD cognitive deficit (MMSE < 26) exhibited a distinguished EV cytokine profile compared to those without cognitive deficit. The findings support the concept of inflammatory pathogenesis in the development and progression of PD and indicate that plasma EV cytokines may serve as PD biomarkers in future.

Keywords: Parkinson’s disease; cytokine; extracellular vesicles; inflammation.

Figure 1

Cytokine levels in plasma extracellular vesicles in patients with Parkinson’s disease (PD) (n = 113) and controls (n = 48). (A) Representative protein blot images of different cytokines, including pro-interleukin (IL)-1β, IL-6, IL-10, tumor necrosis factor (TNF)-α, and transforming growth factor (TGF)-β1. Heat shock protein (HSP)-70 was the protein loading control. (B–F) Quantification data of western blot to compare the TNF-α, IL-10, IL-6, TGF-β1, and pro-IL-1β levels between control and PD subjects. The box-and-whisker plot was presented as median, 1st quartile and 3rd quartile of the box, the 95th and 5th percentile for the upper and lower whisker, ○ for the outliners. n.s., nonsignificant.

Figure 2

Cytokine levels in plasma extracellular vesicles for Parkinson’s disease with Mini-Mental State Examination (MMSE) less than 26 (n = 51) and equal/above 26 (n = 62). (A–E) Comparison of tumor necrosis factor (TNF)-α, interleukin (IL)-10, IL-6, transforming growth factor (TGF)-β1, and pro-IL-1β levels between PD patients with MMSE less than 26 and equal/above 26. Heat shock protein (HSP)-70 was the protein loading control. The box-and-whisker plot was presented as median, 1st quartile and 3rd quartile of the box, the 95th and 5th percentile for the upper and lower whisker, ○ for the outliners.