Abstract
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.
Highlights
Parkinson’s disease (PD) is the second most common neurodegenerative disease [1].The pathological hallmark of PD is the formation of Lewy bodies inside the midbrain dopaminergic neurons
We further investigated the correlation between plasma Extracellular vesicles (EVs) α-synuclein an mographic information of patients and their PD severity
These results indicate that plasma EV α-synuclein is closely associated with the presence of motor symptoms in patients with PD; this association is reconcilable with a contemporary clinical diagnosis of PD, and plasma EV α-synuclein can serve as one of the biomarker panels for diagnosis of PD
Summary
Parkinson’s disease (PD) is the second most common neurodegenerative disease [1]. The pathological hallmark of PD is the formation of Lewy bodies inside the midbrain dopaminergic neurons. Many studies have investigated PD-pathognomonic proteins in the blood or serum as disease biomarkers, but controversial and inconclusive results have been obtained [5]. Exosomes, which are a type of EV with a diameter of 30–100 nm, have attracted increased research attention [6] Owing to their lipid-layered outer membrane, exosomes can cross the blood–brain barrier (BBB) and remain stable in the blood for a long period [7]. This high structural stability prevents the degradation of circulating biomarkers and reflects the intraneuronal condition in the periphery. Considering that α-synuclein may be associated with PD diagnosis, disease progression, and therapeutic response, we hypothesized that α-synuclein transported by plasma EVs could serve as a biomarker for the diagnosis and subtype classification of PD
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