Proteome-based plasma biomarkers for Alzheimer's disease
Proteome-based plasma biomarkers for Alzheimer's disease
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DOI：
10.1093/brain/awl279
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发表时间：
2006-11-01
期刊：
影响因子：
14.5
通讯作者：
Lovestone, S.
中科院分区：
文献类型：
--
作者：
Hye, A.;Lynham, S.;Lovestone, S.
阿尔茨海默病是一种常见的破坏性疾病，目前还没有现成的生物标志物来帮助诊断或监测疾病的进展。已经有人在脑脊液中寻找生物标记物，但以前还没有研究使用双向凝胶电泳联用质谱仪在周围组织中寻找生物标记物。我们使用这种蛋白质组学方法对血浆进行了病例对照研究，以确定与老年对照组相比，疾病状态不同的蛋白质。对于发现阶段的蛋白质组学分析，通过二级服务招募了50名阿尔茨海默氏症患者，并通过初级保健招募了50名正常老年人对照组。为了验证的目的，总共检查了511名阿尔茨海默病和其他神经退行性疾病的受试者和正常的老年对照组。仅凝胶蛋白分布的图像分析就能识别疾病病例，敏感度为56%，特异度为80%。对二维电泳观察到的变化进行的质谱分析发现了一些以前与疾病病理有关的蛋白质，包括补体因子H(CFH)前体和α-2-巨球蛋白(α-M-2)。使用半定量免疫印迹法，CFH和α-M-2的升高被证明是阿尔茨海默病的特异性，并与疾病严重程度相关，尽管有必要进行替代分析来提高敏感性和特异性。这些发现表明，血液可能是阿尔茨海默病生物标志物的丰富来源，CFH与其他蛋白质如α-M-2一起可能是阿尔茨海默病的特异性标志物。
Alzheimer's disease is a common and devastating disease for which there is no readily available biomarker to aid diagnosis or to monitor disease progression. Biomarkers have been sought in CSF but no previous study has used two-dimensional gel electrophoresis coupled with mass spectrometry to seek biomarkers in peripheral tissue. We performed a case-control study of plasma using this proteomics approach to identify proteins that differ in the disease state relative to aged controls. For discovery-phase proteomics analysis, 50 people with Alzheimer's dementia were recruited through secondary services and 50 normal elderly controls through primary care. For validation purposes a total of 511 subjects with Alzheimer's disease and other neurodegenerative diseases and normal elderly controls were examined. Image analysis of the protein distribution of the gels alone identifies disease cases with 56% sensitivity and 80% specificity. Mass spectrometric analysis of the changes observed in two-dimensional electrophoresis identified a number of proteins previously implicated in the disease pathology, including complement factor H (CFH) precursor and alpha-2-macroglobulin (alpha-M-2). Using semi-quantitative immunoblotting, the elevation of CFH and alpha-M-2 was shown to be specific for Alzheimer's disease and to correlate with disease severity although alternative assays would be necessary to improve sensitivity and specificity. These findings suggest that blood may be a rich source for biomarkers of Alzheimer's disease and that CFH, together with other proteins such as alpha-M-2 may be a specific markers of this illness.