Modeling of Pathological Traits in Alzheimer's Disease Based on Systemic Extracellular Signaling Proteome
Modeling of Pathological Traits in Alzheimer's Disease Based on Systemic Extracellular Signaling Proteome
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DOI：
10.1074/mcp.m111.008862
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发表时间：
2011-10-01
影响因子：
7
通讯作者：
Wyss-Coray, Tony
中科院分区：
文献类型：
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作者：
Britschgi, Markus;Rufibach, Kaspar;Wyss-Coray, Tony
对包括阿尔茨海默病在内的慢性脑部疾病的研究通常仅限于脑成像或心理测试。鉴于流行病的上升和对散发性阿尔茨海默病病理途径的认识不足，需要新的工具来确定这种疾病的分子变化。我们假设脑脊液或血浆中特定分泌细胞信号蛋白的水平与阿尔茨海默病大脑的病理变化相关，因此可以用于发现疾病中改变的信号通路。在这里，我们测量了阿尔茨海默病患者和认知正常对照的血浆或脑脊液中细胞通讯蛋白质组亚组的91种蛋白质，以数学模型描述疾病特异性分子特征。我们发现了少量的信号蛋白，它们能够模拟阿尔茨海默病的关键病理标志物，包括脑脊液β-淀粉样蛋白和tau蛋白的水平，并在独立样本中对疾病进行分类。其中几个因素以前曾与阿尔茨海默病有关，支持我们方法的有效性。我们的研究还指出了以前未知的与阿尔茨海默病相关的蛋白质，从而暗示了这种疾病中的新信号通路。Molecular & Cellular Proteomics 10：10.1074/mcp. M111.008862，1-11，2011.
The study of chronic brain diseases including Alzheimer's disease in patients is typically limited to brain imaging or psychometric testing. Given the epidemic rise and insufficient knowledge about pathological pathways in sporadic Alzheimer's disease, new tools are required to identify the molecular changes underlying this disease. We hypothesize that levels of specific secreted cellular signaling proteins in cerebrospinal fluid or plasma correlate with pathological changes in the Alzheimer's disease brain and can thus be used to discover signaling pathways altered in the disease. Here we measured 91 proteins of this subset of the cellular communication proteome in plasma or cerebrospinal fluid in patients with Alzheimer's disease and cognitively normal controls to mathematically model disease-specific molecular traits. We found small numbers of signaling proteins that were able to model key pathological markers of Alzheimer's disease, including levels of cerebrospinal fluid beta-amyloid and tau, and classify disease in independent samples. Several of these factors had previously been implicated in Alzheimer's disease supporting the validity of our approach. Our study also points to proteins which were previously unknown to be associated with Alzheimer's disease thereby implicating novel signaling pathways in this disorder. Molecular & Cellular Proteomics 10: 10.1074/mcp.M111.008862, 1-11, 2011.