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Plasma pS129-?-Synuclein Is a Surrogate Biofluid Marker of Motor Severity and Progression in Parkinson's Disease.

ABSTRACT: Phosphorylated ?-synuclein accounts for more than 90% of ?-synuclein found in Lewy bodies of Parkinson's disease (PD). We aimed to examine whether plasma Ser129-phosphorylated ?-synuclein (pS129-?-synuclein) is a surrogate marker of PD progression. This prospective study enrolled 170 participants (122 PD patients, 68 controls). We measured plasma levels of total and pS129-?-synuclein using immunomagnetic reduction-based immunoassay. PD patients received evaluations of motor and cognition at baseline and at a mean follow-up interval of three years. Changes in the Movement Disorder Society revision of the Unified Parkinson's Disease Rating Scale motor score (MDS-UPDRS part III) and Mini-Mental State Examination (MMSE) score were used to assess motor and cognition progression. Our results showed that plasma levels of total and pS129-?-synuclein were significantly higher in PD patients than controls (total: 1302.3 ± 886.6 fg/mL vs. 77.8 ± 36.6 fg/mL, p < 0.001; pS129-?-synuclein: 12.9 ± 8.7 fg/mL vs. 0.8 ± 0.6 fg/mL, p < 0.001), as was the pS129-?-synuclein/total ?-synuclein ratio (2.8 ± 1.1% vs. 1.1 ± 0.6%, p = 0.01). Among PD patients, pS129-?-synuclein levels were higher with advanced motor stage (p < 0.001) and correlated with MDS-UPDRS part III scores (r = 0.27, 95% CI: 0.09-0.43, p = 0.004). However, we found no remarkable difference between PD patients with and without dementia (p = 0.75). After a mean follow-up of 3.5 ± 2.1 years, PD patients with baseline pS129-?-synuclein > 8.5 fg/mL were at higher risk of motor symptom progression of at least 3 points in the MDS-UPDRS part III scores than those with pS129-?-synuclein < 8.5 fg/mL (p = 0.03, log rank test). In conclusion, our data suggest that plasma pS129-?-synuclein levels correlate with motor severity and progression, but not cognitive decline, in patients with PD.

SUBMITTER: Lin CH

PROVIDER: S-EPMC6832465 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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Plasma pS129-α-Synuclein Is a Surrogate Biofluid Marker of Motor Severity and Progression in Parkinson's Disease.

Lin Chin-Hsien CH Liu Huei-Chun HC Yang Shieh-Yueh SY Yang Kai-Chien KC Wu Chau-Chung CC Chiu Ming-Jang MJ

Journal of clinical medicine 20191003 10

Phosphorylated α-synuclein accounts for more than 90% of α-synuclein found in Lewy bodies of Parkinson's disease (PD). We aimed to examine whether plasma Ser129-phosphorylated α-synuclein (pS129-α-synuclein) is a surrogate marker of PD progression. This prospective study enrolled 170 participants (122 PD patients, 68 controls). We measured plasma levels of total and pS129-α-synuclein using immunomagnetic reduction-based immunoassay. PD patients received evaluations of motor and cognition at base ...[more]

PMID: 31623323

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Project description: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. 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. 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. 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.

Dataset Information

Plasma pS129-?-Synuclein Is a Surrogate Biofluid Marker of Motor Severity and Progression in Parkinson's Disease.

Publications

Plasma pS129-α-Synuclein Is a Surrogate Biofluid Marker of Motor Severity and Progression in Parkinson's Disease.

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