Differential Sialylation of Serpin A1 in the Early Diagnosis of Parkinson's Disease Dementia
Differential Sialylation of Serpin A1 in the Early Diagnosis of Parkinson's Disease Dementia
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DOI：
10.1371/journal.pone.0048783
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发表时间：
2012-11-08
期刊：
影响因子：
3.7
通讯作者：
Otto, Markus
中科院分区：
文献类型：
--
作者：
Jesse, Sarah;Lehnert, Stefan;Otto, Markus
帕金森病（PD）的患病率随着年龄的增长而增加。多达50%的帕金森患者在早期阶段就表现出轻度认知障碍的认知能力下降，这预示着痴呆症的发展，长期来看，多达80%的帕金森患者会出现痴呆症，被称为帕金森病痴呆（PDD）。到目前为止，PD/PDD的诊断是根据临床和神经心理学检查，实验室数据仅用于排除其他疾病。本研究的目的是鉴定PD， PDD和对照（CON）脑脊液（CSF）中可能预测PD痴呆发展的生物标志物。为此，在第一步对18例临床特征良好的患者进行了CSF优化的蛋白质组学方法，随后对84例患者进行了验证。在这里，我们检测了Serpin A1的不同唾液化异构体，作为脑脊液中PD与PDD分化的标志。通过2d免疫印迹，所有PDD患者都能被正确识别（灵敏度100%）。24例PD患者中有10例显示出与PDD相似的Serpin A1亚型，表明该检测方法的特异性为58%。在对照样品中，未检测到额外的异构体。基于这些结果，我们得出结论，Serpin A1的差异唾液化产物是一个有趣的生物标志物，可以指示PD过程中痴呆的发展。引用本文：Jesse S， Lehnert S, Jahn O, Parnetti L， Soininen H等（2012）Serpin A1唾液化在帕金森病痴呆早期诊断中的差异。PLoS ONE 7(11): e48783。doi: 10.1371 / journal.pone.0048783
The prevalence of Parkinson's disease (PD) increases with age. Up to 50% of PD show cognitive decline in terms of a mild cognitive impairment already in early stages that predict the development of dementia, which can occur in up to 80% of PD patients over the long term, called Parkinson's disease dementia (PDD). So far, diagnosis of PD/PDD is made according to clinical and neuropsychological examinations while laboratory data is only used for exclusion of other diseases. The aim of this study was the identification of possible biomarkers in cerebrospinal fluid (CSF) of PD, PDD and controls (CON) which predict the development of dementia in PD. For this, a proteomic approach optimized for CSF was performed using 18 clinically well characterized patients in a first step with subsequent validation using 84 patients. Here, we detected differentially sialylated isoforms of Serpin A1 as marker for differentiation of PD versus PDD in CSF. Performing 2D-immunoblots, all PDD patients could be identified correctly (sensitivity 100%). Ten out of 24 PD patients showed Serpin A1 isoforms in a similar pattern like PDD, indicating a specificity of 58% for the test-procedure. In control samples, no additional isoform was detected. On the basis of these results, we conclude that differentially sialylated products of Serpin A1 are an interesting biomarker to indicate the development of a dementia during the course of PD. Citation: Jesse S, Lehnert S, Jahn O, Parnetti L, Soininen H, et al. (2012) Differential Sialylation of Serpin A1 in the Early Diagnosis of Parkinson's Disease Dementia. PLoS ONE 7(11): e48783. doi:10.1371/journal.pone.0048783