Lysophosphatidylcholine and Amide as Metabolites for Detecting Alzheimer Disease Using Ultrahigh-Performance Liquid Chromatography-Quadrupole Time-of-Flight Mass Spectrometry-Based Metabonomics
Lysophosphatidylcholine and Amide as Metabolites for Detecting Alzheimer Disease Using Ultrahigh-Performance Liquid Chromatography-Quadrupole Time-of-Flight Mass Spectrometry-Based Metabonomics
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DOI：
10.1097/nen.0000000000000116
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发表时间：
2014-10-01
影响因子：
3.2
通讯作者：
Wu, Qunhong
中科院分区：
文献类型：
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作者：
Cui, Yu;Liu, Xiuqin;Wu, Qunhong
阿尔茨海默病（AD）可以通过临床和神经心理学测试以及尸检进行诊断，但在认知障碍的早期阶段，没有简单有效的诊断方法来检测患者的生物标志物。早期代谢改变，可能有助于AD的诊断尚未彻底探讨。我们应用非靶向代谢组学方法，采用超高效液相色谱-四极杆飞行时间质谱分析46例AD患者和36例健康对照的血清和尿液样本。使用多变量分析处理代谢物谱，以鉴定潜在代谢物，并使用串联质谱法进一步确认。此外，还使用超高效液相色谱质谱法对潜在重要的生物标志物进行定量。然后选择独立样品以验证鉴定的生物标志物。健康对照组和AD患者之间存在明显的差异; AD患者样本存在氨基酸和磷脂代谢紊乱以及棕榈酰胺失调。受试者操作特征曲线和定量结果表明，棕榈酰胺、溶血磷脂酰胆碱（LysoPC，18：0）、LysoPC（18：2）、L-谷氨酰胺和5-L-谷氨酰甘氨酸是最佳代谢产物。此外，验证研究中棕榈酰胺、LysoPC（18：2）和5-L-谷氨酰甘氨酸的曲线下面积分别为0.714、0.996和0.734。这些数据阐明了与AD相关的代谢改变，并提出了AD诊断的新生物标志物，从而允许旨在预防疾病进展的早期干预。
Alzheimer disease (AD) can be diagnosed by clinical and neuropsychologic tests and at autopsy, but there are no simple effective diagnostic methods for detecting biomarkers in patients at early stages of cognitive impairment. Early metabolic alterations that may facilitate AD diagnosis have not been thoroughly explored. We applied a nontargeted metabonomic approach using ultrahigh-performance liquid chromatography-quadrupole time-of-flight mass spectrometry to analyze serum and urine samples from 46 patients with AD and 36 healthy controls. Metabolite profiles were processed using multivariate analysis to identify potential metabolites, which were further confirmed using tandem mass spectrometry. Ultrahigh-performance liquid chromatography mass spectrometry methods were additionally used to quantify potentially important biomarkers. Independent samples were then selected to validate the identified biomarkers. There was a clear separation between healthy controls and AD patients; AD patient samples had disordered amino acid and phospholipid metabolism and dysregulated palmitic amide. Receiver operator characteristic curve and quantification suggested that palmitic amide, lysophosphatidylcholine (LysoPC, 18: 0), LysoPC(18: 2), L-glutamine, and 5-L-glutamylglycine were the optimal metabolites. In addition, areas under the curve from the palmitic amide, LysoPC(18: 2), and 5-L-glutamylglycine in the validation study were 0.714, 0.996, and 0.734, respectively. These data elucidate the metabolic alterations associated with AD and suggest new biomarkers for AD diagnosis, thereby permitting early intervention designed to prevent disease progression.