未经药物治疗的帕金森病患者脑脊液中致病蛋白的相关水平

Correlated levels of cerebrospinal fluid pathogenic proteins in drug-naïve Parkinson's disease.

作者信息

Murakami Hidetomo, Tokuda Takahiko, El-Agnaf Omar M A, Ohmichi Takuma, Miki Ayako, Ohashi Hideaki, Owan Yoshiyuki, Saito Yu, Yano Satoshi, Tsukie Tamao, Ikeuchi Takeshi, Ono Kenjiro

机构信息

Department of Neurology, School of Medicine, Showa University, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo, 142-8666, Japan.

Department of Molecular Pathobiology of Brain Diseases, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kawaramachi-Hirokoji, Kamikyo-ku, Kyoto, 602-8566, Japan.

出版信息

BMC Neurol. 2019 Jun 4;19(1):113. doi: 10.1186/s12883-019-1346-y.

DOI:10.1186/s12883-019-1346-y

PMID:31164098

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6549316/

Abstract

BACKGROUND AND AIM

Toxic oligomeric α-synuclein (αS; O-αS) has been suggested to play a central role in the pathogenesis of Lewy body diseases such as Parkinson's disease (PD). Cerebrospinal fluid (CSF) levels of αS, O-αS, total and phosphorylated tau, and amyloid β 1-42 (Aβ1-42) are thought to reflect the pathophysiology or clinical symptoms in PD. In this study, we examined correlations of the CSF levels of these proteins with the clinical symptoms, and with each other in drug-naïve patients with PD.

METHODS

Twenty-seven drug-naïve patients with PD were included. Motor and cognitive functions were assessed using the Unified Parkinson's Disease Rating Scale (UPDRS), Montreal Cognitive Assessment (MoCA), and Neurobehavioral Cognitive Status Examination (COGNISTAT). CSF levels of total αS, O-αS, Aβ1-42, total tau and tau phosphorylated at threonine 181 (P-tau181p) were measured. CSF levels of these proteins were compared with clinical assessments from the UPDRS, MoCA and COGNISTAT using Spearman correlation analysis. Spearman correlation coefficients among CSF protein levels were also evaluated.

RESULTS

CSF levels of αS were negatively correlated with UPDRS part III (motor score) (p < 0.05) and bradykinesia (p < 0.01), and positively correlated with COGNISTAT subtest of judgement (p < 0.01) and CSF levels of Aβ1-42 (p < 0.001), total tau (p < 0.001) and P-tau181p (p < 0.01). Lower CSF levels of Aβ1-42, total tau and P-tau181p were significantly related to worsening of some motor and/or cognitive functions. The CSF level of O-αS showed no correlation with any motor and cognitive assessments or with CSF levels of the other proteins.

CONCLUSION

CSF levels of αS are correlated with some clinical symptoms and CSF levels of other pathogenic proteins in drug-naïve PD patients. These correlations suggest a central role for interaction and aggregation of αS with Aβ1-42, tau, and phosphorylated tau in the pathogenesis of PD. Although O-αS has been shown to have neurotoxic effects, CSF levels do not reflect clinical symptoms or levels of other proteins in cross-sectional assessment.

摘要

背景与目的

毒性寡聚α-突触核蛋白（αS；O-αS）被认为在路易体病如帕金森病（PD）的发病机制中起核心作用。脑脊液（CSF）中αS、O-αS、总tau蛋白和磷酸化tau蛋白以及淀粉样β1-42（Aβ1-42）的水平被认为反映了PD的病理生理学或临床症状。在本研究中，我们检测了这些蛋白的脑脊液水平与临床症状之间以及在未接受过药物治疗的PD患者中这些蛋白之间的相关性。

方法

纳入27例未接受过药物治疗的PD患者。使用统一帕金森病评定量表（UPDRS）、蒙特利尔认知评估量表（MoCA）和神经行为认知状态检查量表（COGNISTAT）评估运动和认知功能。检测脑脊液中总αS、O-αS、Aβ1-42、总tau蛋白和苏氨酸181位点磷酸化的tau蛋白（P-tau181p）的水平。使用Spearman相关分析将这些蛋白的脑脊液水平与UPDRS、MoCA和COGNISTAT的临床评估结果进行比较。还评估了脑脊液蛋白水平之间的Spearman相关系数。

结果

脑脊液中αS水平与UPDRS第三部分（运动评分）（p<0.05）和运动迟缓（p<0.01）呈负相关，与COGNISTAT判断子测试（p<0.01）以及脑脊液中Aβ1-42水平（p<0.001）、总tau蛋白水平（p<0.001）和P-tau181p水平（p<0.01）呈正相关。脑脊液中Aβ1-42、总tau蛋白和P-tau181p水平较低与某些运动和/或认知功能恶化显著相关。O-αS的脑脊液水平与任何运动和认知评估或其他蛋白的脑脊液水平均无相关性。

结论

在未接受过药物治疗的PD患者中，脑脊液中αS水平与一些临床症状以及其他致病蛋白的脑脊液水平相关。这些相关性表明αS与Aβ1-42、tau蛋白和磷酸化tau蛋白的相互作用和聚集在PD发病机制中起核心作用。尽管O-αS已被证明具有神经毒性作用，但在横断面评估中，脑脊液水平并未反映临床症状或其他蛋白的水平。