Plasma Exosomal Brain-Derived Neurotrophic Factor Correlated with the Postural Instability and Gait Disturbance–Related Motor Symptoms in Patients with Parkinson’s Disease

Chung, Chen-Chih; Huang, Pai Hao; Chan, Lung; Chen, Jia Hung; Chien, Li‐Nien; Hong, Chien Tai

doi:10.3390/diagnostics10090684

Cited by 22 publications

(20 citation statements)

References 46 publications

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“…A growing body of evidence suggests that sEVs might be useful as biomarkers in many diseases [ 102 , 104 , 105 , 106 ], as well as prognostic agents providing information about the phase of disease or predicted therapy outcomes [ 107 , 108 , 109 ]; sEVs transfer specific cargo components depending on the cell of origin, and ensure a safe environment for transported compounds. This allows their delivery to both neighboring and distant cells, which is an important modality of communication between tissues and organs.…”

Section: Discussionmentioning

confidence: 99%

The Emerging Role of Small Extracellular Vesicles in Inflammatory Airway Diseases

et al. 2021

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Extracellular vesicles (EVs) are produced and released by all cells and are present in all body fluids. They exist in a variety of sizes, however, small extracellular vesicles (sEVs), the EV subset with a size range from 30 to 150 nm, are of current interest. By transporting a complex cargo that includes genetic material, proteins, lipids, and signaling molecules, sEVs can alter the state of recipient cells. The role of sEVs in mediating inflammatory processes and responses of the immune system is well-documented, and adds another layer of complexity to our understanding of frequent diseases, including chronic rhinosinusitis (CRS), asthma, chronic obstructive pulmonary disease (COPD), and upper airway infections. In these diseases, two aspects of sEV biology are of particular interest: (1) sEVs might be involved in the etiopathogenesis of inflammatory airway diseases, and might emerge as attractive therapeutic targets, and (2) sEVs might be of diagnostic or prognostic relevance. The purpose of this review is to outline the biological functions of sEVs and their capacity to both augment and attenuate inflammation and immune response in the context of pathogen invasion, CRS, asthma, and COPD.

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Section: Discussionmentioning

confidence: 99%

The Emerging Role of Small Extracellular Vesicles in Inflammatory Airway Diseases

et al. 2021

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“…Isolated EVs were validated by detecting the presence of tetraspanins (CD9, CD81 and CD63), the presence of EV inner component (Tumor susceptibility gene 101), and negative of mitochondrial protein (cytochrome c), and their sizes were determined through nanoparticle tracking with a peak around 100nM. The validation details have been described in previous studies from our PD cohort [ 22 , 23 ].…”

Section: Methodsmentioning

confidence: 99%

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

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Chung

Chen

et al. 2021

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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.

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“…Isolated EVs were validated by detecting tetraspanins (CD9, CD81, and CD63), Inner components of EVs (tumor susceptibility gene 101), the negative segments of mitochondrial protein (cytochrome c), and their sizes were determined through nanoparticle tracking with a peak of approximately 100 nM. Details on the validation were described in our previous studies involving this PD cohort [ 12 , 13 ].…”

Section: Methodsmentioning

confidence: 99%

“…EV-borne biomarkers, including proteins [ 11 , 12 , 13 ] and microRNA [ 14 , 15 ], have also been extensively examined in the context of PD. Cellular α-synuclein is transported to exosomes via the endosome pathway [ 16 ].…”

Section: Introductionmentioning

confidence: 99%

Plasma Extracellular Vesicle α-Synuclein Level in Patients with Parkinson’s Disease

et al. 2021

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Background: The most established pathognomonic protein of Parkinson’s disease (PD), α-synuclein, is extensively investigated for disease diagnosis and prognosis; however, investigations into whether the free form of α-synuclein in the blood functions as a PD biomarker have not been fruitful. Extracellular vesicles (EVs) secreted from cells and present in blood transport molecules are novel platforms for biomarker identification. In blood EVs, α-synuclein originates predominantly from the brain without the interference of the blood–brain barrier. The present study investigated the role of plasma EV-borne α-synuclein as a biomarker of PD. Methods: Patients with mild to moderate stages of PD (n = 116) and individuals without PD (n = 46) were recruited to serve as the PD study group and the control group, respectively. Plasma EVs were isolated, and immunomagnetic reduction–based immunoassay was used to assess EV α-synuclein levels. Conventional statistical analysis was performed using SPSS 25.0, and p < 0.05 was considered significant. Results: Compared with controls, we observed significantly lower plasma EV α-synuclein levels in the patients with PD (PD: 56.0 ± 3.7 fg/mL vs. control: 74.5 ± 4.3 fg/mL, p = 0.009), and the significance remained after adjustment for age and sex. Plasma EV α-synuclein levels in the patients with PD did not correlate with age, disease duration, Part I and II scores of the Unified Parkinson’s Disease Rating Scale (UPDRS), or the Mini-Mental State Examination scores. However, such levels were significantly correlated with UPDRS Part III score, which assesses motor dysfunction. Furthermore, the severity of akinetic-rigidity symptoms, but not tremor, was inversely associated with plasma EV α-synuclein level. Conclusion: Plasma EV α-synuclein was significantly different between the control and PD group and was associated with akinetic-rigidity symptom severity in patients with PD. This study corroborates the possible diagnostic and subtyping roles of plasma EV α-synuclein in patients with PD, and it further provides a basis for this protein’s clinical relevance and feasibility as a PD biomarker.

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Plasma Exosomal Brain-Derived Neurotrophic Factor Correlated with the Postural Instability and Gait Disturbance–Related Motor Symptoms in Patients with Parkinson’s Disease

Cited by 22 publications

References 46 publications

The Emerging Role of Small Extracellular Vesicles in Inflammatory Airway Diseases

The Emerging Role of Small Extracellular Vesicles in Inflammatory Airway Diseases

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

Plasma Extracellular Vesicle α-Synuclein Level in Patients with Parkinson’s Disease

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