Decreased α-synuclein in cerebrospinal fluid of aged individuals and subjects with Parkinson's disease
Decreased α-synuclein in cerebrospinal fluid of aged individuals and subjects with Parkinson's disease
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DOI：
10.1016/j.bbrc.2006.08.024
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发表时间：
2006-10-13
影响因子：
3.1
通讯作者：
El-Agnaf, Omar M. A.
中科院分区：
文献类型：
--
作者：
Tokuda, Takahiko;Salem, Sultan A.;El-Agnaf, Omar M. A.
大量的生化、病理和遗传学证据表明，α -突触核蛋白（α -syn）的代谢在帕金森病（PD）的发病机制中起着至关重要的作用。为了检验脑脊液中α -syn的定量是否对PD的诊断有潜在的信息价值，我们开发了一种特异性的ELISA系统，并测量了33名PD患者（根据英国PD协会脑库标准诊断）和38名对照受试者（包括9名神经健康个体）脑脊液中α -syn的浓度。我们发现，即使在性别和年龄调整后，PD患者脑脊液中的α -syn水平也明显低于对照组（p < 0.0001）。年龄与较低的a-syn水平独立相关。Logistic回归分析显示，脑脊液α -syn减少是PD的重要预测因子，不只是年龄和性别（ROC曲线下面积，c = 0.882）。此外，我们观察到，即使在调整年龄后，71名在世受试者的CSF α -syn水平与分配的Hoehn和Yahr评分之间也存在密切的负相关（P < 0.0001）。这些发现确定了脑脊液α -syn的定量是一种潜在的实验室标记物，可以帮助PD的临床诊断。(c) 2006爱思唯尔公司版权所有。
There is ample biochemical, pathological, and genetic evidence that the metabolism of alpha-synuclein (alpha-syn) plays a crucial role in the pathogenesis of Parkinson disease (PD). To examine whether quantification of alpha-syn in cerebrospinal fluid (CSF) is potentially informative in the diagnosis of PD, we developed a specific ELISA system and measured the concentration of alpha-syn in CSF from 33 patients with PD (diagnosed according to UK PD Society Brain Bank criteria) and 38 control subjects including 9 neurologically healthy individuals. We found that PD patients had significantly lower alpha-syn levels in their CSF than the control groups (p < 0.0001) even after adjusting for gender and age. Age was independently associated with lower a-syn levels. Logistic regression analysis showed that reduction in CSF alpha-syn served as a significant predictor of PD beyond age and gender alone (area under ROC curve, c = 0.882). Furthermore, we observed a close inverse correlation between alpha-syn levels in CSF and assigned Hoehn and Yahr score in this cohort of 71 living subjects (P < 0.0001), even after adjusting for age. These findings identify in the quantification of alpha-syn from CSF a potential laboratory marker to aid the clinical diagnosis of PD. (c) 2006 Elsevier Inc. All rights reserved.