Blood-based diagnosis of Alzheimer's disease using fingerprinting metabolomics based on hydrophilic interaction liquid chromatography with mass spectrometry and multivariate statistical analysis
Blood-based diagnosis of Alzheimer's disease using fingerprinting metabolomics based on hydrophilic interaction liquid chromatography with mass spectrometry and multivariate statistical analysis
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DOI：
10.1016/j.jchromb.2014.10.022
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发表时间：
2015-01-01
影响因子：
3
通讯作者：
Toyo'oka, Toshimasa
中科院分区：
文献类型：
--
作者：
Inoue, Koichi;Tsuchiya, Hirofumi;Toyo'oka, Toshimasa
阿尔茨海默病（AD）的早期和明确诊断可以为患者提供更好和更有针对性的治疗和/或预防。在AD的诊断生物标志物中，血液样本代表了比脑脊液更无创、更便宜和可接受的重复测量来源。本研究提出了指纹代谢组学方法，以解决亲水相互作用液相色谱/质谱（HILIC/MS）在血液基础上诊断AD的难题。这些血浆样本是根据这些病理学检查从死后标本中选择的。首先，我们比较了这些HILIC柱用于使用合并血浆的非靶向代谢测定。使用这些色谱图的重复性进行这七个色谱柱的主成分分析图，并可用于通过三维分散、贡献标准差和检测次数可视化数据集的趋势。基于这些结果，TSK-Amide 80和TSKgel-NH 2色谱柱用作基于血液的AD代谢组学的可靠HILIC/MS测定，其显示MS色谱图中AD病理学的代谢特征，范围为1182至2284种化合物。使用正交偏最小二乘判别分析评价了总共54个峰以识别有用的离子信号候选者。然后使用HILIC串联MS测定通过受试者操作特征曲线和线性判别分析对这些峰进行特异性分析，以诊断定义的AD。指纹代谢组学可以克服以往基于血液的AD诊断的局限性，并直接从原始数据中评估特定的比较统计值。(C)2014爱思唯尔有限公司版权所有。
Early and definitive diagnosis of Alzheimer's disease (AD) can lead to a better and more-targeted treatment and/or prevention for patients. In the diagnostic biomarkers of AD, the blood sample represents a more non-invasive, inexpensive and acceptable sources for repeated measurements than the cerebrospinal fluid. In this study, the fingerprinting metabolomics was proposed for the challenge of the blood-based diagnosis of defined AD by hydrophilic interaction liquid chromatography mass spectrometry (HILIC/MS). These plasma samples were selected from postmortem specimens based on these pathological examinations. Firstly, we compared these HILIC columns for the non-targeted metabolic assay using pooled plasma. The principal component analysis plot of these seven columns was performed using the repeatability of these chromatograms, and can be used to visualize trends in data sets by three-dimensional dispersion, contributory standard deviation and the number of detections. Based on these results, TSK-Amide 80 and TSKgel-NH2 columns are used as a reliable HILIC/MS assay of blood-based AD metabolomics that showed metabolic profiling of the AD pathology in MS chromatograms that ranged from 1182 to 2284 compounds. A total of 54 peaks were evaluated in order to identify useful ion signal candidates using an orthogonal partial least-squares-discriminant analysis. These peaks were then specifically analyzed using the HILIC-tandem MS assay by a receiver operating characteristic curve and linear discriminant analysis for the diagnosis of the defined AD. The fingerprinting metabolomics can overcome the limitations of previous challenging blood-based diagnosis of AD, and directly evaluates the specific comparative statistical values from the raw data. (C) 2014 Elsevier B.V. All rights reserved.