Comparative proteomic analysis of intra- and interindividual variation in human cerebrospinal fluid
Comparative proteomic analysis of intra- and interindividual variation in human cerebrospinal fluid
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DOI：
10.1074/mcp.m500207-mcp200
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发表时间：
2005-12-01
影响因子：
7
通讯作者：
Holtzman, DM
中科院分区：
文献类型：
--
作者：
Hu, Y;Malone, JP;Holtzman, DM
脑脊液（CSF）是包括阿尔茨海默病（AD）在内的许多中枢神经系统疾病的生物标志物的潜在来源。在比较个体之间的CSF样本以识别疾病相关蛋白的模式之前，重要的是在短时间内检查个体内的变化，以便可以更好地解释个体之间CSF的潜在变化以及给定个体内的变化。在这项研究中，我们分析了12个CSF样本，由来自6个个体的成对样本组成，间隔2周获得。使用多亲和耗竭、二维DIGE和串联质谱法。对于每个个体，鉴定了在两个时间点之间丰度变化的许多蛋白质。其中一些蛋白质通常在多个个体中鉴定。更重要的是，尽管存在个体内变异，但蛋白质组谱的分层聚类和多维缩放分析显示，来自同一个体的两个CSF样本聚集在一起最接近，并且受试者间变异性远大于受试者内变异性。在6名受试者中，4名认知正常受试者和2名极轻度痴呆受试者之间的比较也产生了一些在先前AD生物标志物研究中已鉴定的蛋白质。这些结果验证了我们的方法，确定不同的蛋白质组学档案的CSF样本，并有重要意义的设计CSF生物标志物研究AD和其他中枢神经系统疾病。
Cerebrospinal fluid (CSF) is a potential source of biomarkers for many disorders of the central nervous system, including Alzheimer disease (AD). Prior to comparing CSF samples between individuals to identify patterns of disease-associated proteins, it is important to examine variation within individuals over a short period of time so that one can better interpret potential changes in CSF between individuals as well as changes within a given individual over a longer time span. In this study, we analyzed 12 CSF samples, composed of pairs of samples from six individuals, obtained 2 weeks apart. Multiaffinity depletion, two-dimensional DIGE, and tandem mass spectrometry were used. A number of proteins whose abundance varied between the two time points was identified for each individual. Some of these proteins were commonly identified in multiple individuals. More importantly, despite the intraindividual variations, hierarchical clustering and multidimensional scaling analysis of the proteomic profiles revealed that two CSF samples from the same individual cluster the closest together and that the between-subject variability is much larger than the within-subject variability. Among the six subjects, comparison between the four cognitively normal and the two very mildly demented subjects also yielded some proteins that have been identified in previous AD biomarker studies. These results validate our method of identifying differences in proteomic profiles of CSF samples and have important implications for the design of CSF biomarker studies for AD and other central nervous system disorders.