Sako Wataru, Murakami Nagahisa, Izumi Yuishin, Kaji Ryuji
Department of Clinical Neuroscience, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima, Japan; Center for Neurosciences, The Feinstein Institute for Medical Research, Manhasset, New York, USA.
Mov Disord. 2014 Nov;29(13):1599-605. doi: 10.1002/mds.26036. Epub 2014 Sep 25.
Alpha-synuclein plays a key role in the pathology of synucleinopathies including Parkinson's disease (PD) and multiple system atrophy (MSA). However, whether alpha-synuclein level in cerebrospinal fluid (CSF) could distinguish synucleinopathies from progressive supranuclear palsy (PSP) is still a contentious issue. A comprehensive literature search yielded nine eligible studies. We expressed the between-group difference of the concentration of alpha-synuclein in CSF as the standardized mean difference. The proportion of variation attributable to heterogeneity was computed and expressed as I(2) . Nine studies involved 537 controls, 843 PD, 130 MSA, and 98 PSP patients. The overall effect of PD on alpha-synuclein in CSF was significantly different from normal control or disease control (standardized mean difference = -0.67, P < 0.00001). These studies were heterogeneous (I(2) = 40%). Alpha-synuclein in CSF in MSA was significantly reduced relative to controls with heterogeneous studies (standardized mean difference = -0.75, P < 0.0001; I(2) = 62%). In contrast, no significant difference of alpha-synuclein in CSF was observed between PSP and controls with heterogeneous studies (standardized mean difference = -0.28, P = 0.13; I(2) = 53%). Alpha-synuclein in CSF was significantly reduced in synucleinopathies compared with PSP ("PD vs. PSP": standardized mean difference = -0.38, P = 0.001; "MSA vs. PSP": standardized mean difference = -0.66, P < 0.00001). The included studies were homogeneous (I(2) = 0%). Our study showed that alpha-synuclein levels in CSF in synucleinopathies was significantly lower than in PSP. This finding provides insights into the pathophysiological difference between synucleinopathies and PSP as well as possibility of development of a tool for differential diagnosis between MSA and PSP using enzyme-linked immunosorbent assay (ELISA) and similar methods.
α-突触核蛋白在包括帕金森病（PD）和多系统萎缩（MSA）在内的突触核蛋白病病理学中起关键作用。然而，脑脊液（CSF）中的α-突触核蛋白水平能否将突触核蛋白病与进行性核上性麻痹（PSP）区分开来仍是一个有争议的问题。全面的文献检索产生了9项符合条件的研究。我们将CSF中α-突触核蛋白浓度的组间差异表示为标准化均数差。计算归因于异质性的变异比例并表示为I²。9项研究涉及537名对照、843名PD患者、130名MSA患者和98名PSP患者。PD对CSF中α-突触核蛋白的总体影响与正常对照或疾病对照有显著差异（标准化均数差=-0.67，P<0.00001）。这些研究存在异质性（I²=40%）。与对照相比，MSA患者CSF中的α-突触核蛋白显著降低，研究存在异质性（标准化均数差=-0.75，P<0.0001；I²=62%）。相比之下，在存在异质性的研究中，PSP患者与对照之间CSF中的α-突触核蛋白无显著差异（标准化均数差=-0.28，P=0.13；I²=53%）。与PSP相比，突触核蛋白病患者CSF中的α-突触核蛋白显著降低（“PD与PSP”：标准化均数差=-0.38，P=0.001；“MSA与PSP”：标准化均数差=-0.66，P<0.00001）。纳入的研究具有同质性（I²=0%）。我们的研究表明，突触核蛋白病患者CSF中的α-突触核蛋白水平显著低于PSP患者。这一发现为突触核蛋白病与PSP之间的病理生理差异以及使用酶联免疫吸附测定（ELISA）和类似方法开发MSA与PSP鉴别诊断工具的可能性提供了见解。
