Plasma pS129-α-Synuclein Is a Surrogate Biofluid Marker of Motor Severity and Progression in Parkinson's Disease
Plasma pS129-α-Synuclein Is a Surrogate Biofluid Marker of Motor Severity and Progression in Parkinson's Disease
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DOI：
10.3390/jcm8101601
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发表时间：
2019-10-01
影响因子：
3.9
通讯作者：
Chiu, Ming-Jang
中科院分区：
文献类型：
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作者：
Lin, Chin-Hsien;Liu, Huei-Chun;Chiu, Ming-Jang
磷酸化 α-突触核蛋白占帕金森病 (PD) 路易体中发现的 α-突触核蛋白的 90% 以上。我们的目的是检查血浆 Ser129-磷酸化 α-突触核蛋白 (pS129-α-突触核蛋白) 是否是 PD 进展的替代标志物。这项前瞻性研究招募了 170 名参与者（122 名 PD 患者，68 名对照者）。我们使用基于免疫磁还原的免疫测定法测量了总 pS129-α-突触核蛋白和 pS129-α-突触核蛋白的血浆水平。 PD 患者在基线和平均随访三年期间接受运动和认知评估。运动障碍协会修订的统一帕金森病评定量表运动评分（MDS-UPDRS 第 III 部分）和简易精神状态检查（MMSE）评分的变化用于评估运动和认知进展。我们的结果显示，PD 患者的血浆总水平和 pS129-α-突触核蛋白水平显着高于对照组（总计：1302.3 +/- 886.6 fg/mL 对比 77.8 +/- 36.6 fg/mL，p < 0.001；pS129-α-突触核蛋白：12.9 +/- 8.7 fg/mL 对比 0.8 +/- 0.6 fg/mL，p < 0.001），pS129-α-突触核蛋白/总 α-突触核蛋白比率也是如此（2.8 +/- 1.1% 与 1.1 +/- 0.6%，p = 0.01）。在 PD 患者中，运动阶段晚期的 pS129-α-突触核蛋白水平较高 (p < 0.001)，并且与 MDS-UPDRS 第 III 部分评分相关 (r = 0.27，95% CI：0.09-0.43，p = 0.004)。然而，我们发现患有和不患有痴呆症的 PD 患者之间没有显着差异 (p = 0.75)。平均随访 3.5 +/- 2.1 年后，基线 pS129-α-突触核蛋白 > 8.5 fg/mL 的 PD 患者在 MDS-UPDRS 第 III 部分评分中运动症状进展的风险高于 pS129-α-突触核蛋白 < 8.5 fg/mL 的患者（p = 0.03，对数秩检验）。总之，我们的数据表明，PD 患者血浆 pS129-α-突触核蛋白水平与运动严重程度和进展相关，但与认知能力下降无关。
Phosphorylated alpha-synuclein accounts for more than 90% of alpha-synuclein found in Lewy bodies of Parkinson's disease (PD). We aimed to examine whether plasma Ser129-phosphorylated alpha-synuclein (pS129-alpha-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-alpha-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-alpha-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-alpha-synuclein: 12.9 +/- 8.7 fg/mL vs. 0.8 +/- 0.6 fg/mL, p < 0.001), as was the pS129-alpha-synuclein/total alpha-synuclein ratio (2.8 +/- 1.1% vs. 1.1 +/- 0.6%, p = 0.01). Among PD patients, pS129-alpha-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-alpha-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-alpha-synuclein < 8.5 fg/mL (p = 0.03, log rank test). In conclusion, our data suggest that plasma pS129-alpha-synuclein levels correlate with motor severity and progression, but not cognitive decline, in patients with PD.