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.

Rifaximin Modifies Gut Microbiota and Attenuates Inflammation in Parkinson’s Disease: Preclinical and Clinical Studies

“…Furthermore, systemic inflammation leads to the impairment of the BBB, thus inducing the infiltration of immune cells into the brain and activating microglia-dependent neuroinflammation [ 25 , 56 ]. Studies have reported the presence of elevated proinflammatory cytokine levels in the serum and plasma extracellular vesicles of patients with PD [ 57 , 58 , 59 ]. In the present study, rifaximin treatment significantly altered GM and downregulated blood proinflammatory cytokine levels.…”

Probiotics treatment for Parkinson disease: a systematic review and meta-analysis of clinical trials

“…Systemic inflammation also contributed to an increase in the risk of PD [ 51 ]. PwP exhibited elevated blood cytokine levels in serum and plasma extracellular vesicles compared with healthy controls [ 52 , 53 ]. (Gut dysbiosis is a substantial risk factor of elevated systemic inflammation through the destruction of the intestinal epithelial membrane and the entrance of pathogens and toxins from the intestinal lumen into the systemic circulation [ 54 ].…”

Extracellular vesicles in the study of Alzheimer's and Parkinson's diseases: Methodologies applied from cells to biofluids

“…The levels of other plasma exosomal proteins, as the prion protein, apolipoprotein J (APOJ), ApoA1, CR1 subcomponent, cytokines, insulin receptor substrate 1 and proteasome complex proteins and several immunologic‐associated EVs surface markers, were also capable to distinguish PD cases from controls, while no differences were found for neurofilament light chain or BDNF levels (Anastasi et al, 2021; Chan et al, 2021; Chou et al, 2020; Chung, Chan, et al, 2020; Chung, Huang, et al, 2020; Kitamura et al, 2018; Leng et al, 2020; Vacchi et al, 2020; Vacchi et al, 2021). It was likewise reported that the levels of plasma NDEVs were increased in PD when compared with Controls (Ohmichi et al, 2019).…”