Metabolomics in early Alzheimer's disease: identification of altered plasma sphingolipidome using shotgun lipidomics.
Metabolomics in early Alzheimer's disease: identification of altered plasma sphingolipidome using shotgun lipidomics.
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早期阿尔茨海默病的代谢组学：使用鸟枪脂质组学鉴定改变的血浆鞘脂组。
DOI：
10.1371/journal.pone.0021643
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Kaddurah-Daouk R
中科院分区：
文献类型：
--
作者：
Han X;Rozen S;Boyle SH;Hellegers C;Cheng H;Burke JR;Welsh-Bohmer KA;Doraiswamy PM;Kaddurah-Daouk R
血浆生物标志物的发展有助于阿尔茨海默病（AD）的早期发现、风险评估和治疗监测。神经酰胺和鞘磷脂的改变被认为在淀粉样变和炎症应激相关的神经元凋亡中起作用；然而，很少有研究使用具有准确性、灵敏度和可重复性的分析平台对阿尔茨海默病血浆中的鞘脂组进行全面分析。我们前瞻性地分析了26名AD患者（平均MMSE 21）和26名认知正常对照者的血浆，采用基于多维质谱的散弹枪脂质组学方法，以确定800多种脂质分子种类的水平。然后将这些数据与诊断、载脂蛋白E4基因型和认知表现相关联。阿尔茨海默病患者的血浆鞘脂水平发生了显著变化。在测试的33种鞘磷脂中，8种分子种，特别是含有长脂肪链（如22和24碳原子）的分子种，与对照组相比，AD显著降低（p<0.05）。2种神经酰胺（N16:0和N21:0）在AD中显著升高（p<0.05），其他5种神经酰胺的升高趋势相似，但较弱。在AD患者和对照组中，含有相同脂肪酰基链的神经酰胺与鞘磷脂的比例有显著差异。MMSE评分与N20:2 SM和OH-N25:0神经酰胺的质量水平改变相关（p<0.004），但在轻度和中度AD中观察到脂质异常。在AD受试者中，也存在基因型特异性差异。在这项前瞻性研究中，我们使用了一个敏感的多模态平台来识别和表征阿尔茨海默病血浆中鞘磷脂和神经酰胺质量水平基本一致但相反的破坏模式。鉴于脑鞘脂在神经元功能中的作用，我们的研究结果为阿尔茨海默病鞘脂组和代谢组学特征作为外周生物标志物的潜在应用提供了新的见解。
The development of plasma biomarkers could facilitate early detection, risk assessment and therapeutic monitoring in Alzheimer's disease (AD). Alterations in ceramides and sphingomyelins have been postulated to play a role in amyloidogensis and inflammatory stress related neuronal apoptosis; however few studies have conducted a comprehensive analysis of the sphingolipidome in AD plasma using analytical platforms with accuracy, sensitivity and reproducibility. We prospectively analyzed plasma from 26 AD patients (mean MMSE 21) and 26 cognitively normal controls in a non-targeted approach using multi-dimensional mass spectrometry-based shotgun lipidomics to determine the levels of over 800 molecular species of lipids. These data were then correlated with diagnosis, apolipoprotein E4 genotype and cognitive performance. Plasma levels of species of sphingolipids were significantly altered in AD. Of the 33 sphingomyelin species tested, 8 molecular species, particularly those containing long aliphatic chains such as 22 and 24 carbon atoms, were significantly lower (p<0.05) in AD compared to controls. Levels of 2 ceramide species (N16:0 and N21:0) were significantly higher in AD (p<0.05) with a similar, but weaker, trend for 5 other species. Ratios of ceramide to sphingomyelin species containing identical fatty acyl chains differed significantly between AD patients and controls. MMSE scores were correlated with altered mass levels of both N20:2 SM and OH-N25:0 ceramides (p<0.004) though lipid abnormalities were observed in mild and moderate AD. Within AD subjects, there were also genotype specific differences. In this prospective study, we used a sensitive multimodality platform to identify and characterize an essentially uniform but opposite pattern of disruption in sphingomyelin and ceramide mass levels in AD plasma. Given the role of brain sphingolipids in neuronal function, our findings provide new insights into the AD sphingolipidome and the potential use of metabolomic signatures as peripheral biomarkers.
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影响因子：
--
作者：
De Meyer, Geert;Shapiro, Fred;Vanderstichele, Hugo;Vanmechelen, Eugeen;Engelborghs, Sebastiaan;De Deyn, Peter Paul;Coart, Els;Hansson, Oskar;Minthon, Lennart;Zetterberg, Henrik;Blennow, Kaj;Shaw, Leslie;Trojanowski, John Q.
通讯作者：
Trojanowski, John Q.
影响因子：
6.7
作者：
通讯作者：
--
影响因子：
2.9
作者：
Jiang, Xuntian;Cheng, Hua;Han, Xianlin
通讯作者：
Han, Xianlin
影响因子：
14
作者：
Brookmeyer, Ron;Johnson, Elizabeth;Arrighi, H. Michael
通讯作者：
Arrighi, H. Michael
DOI：
10.1016/j.jasms.2005.11.003
发表时间：
2006-02-01
影响因子：
3.2
作者：
Han, XL;Yang, K;Gross, RW
通讯作者：
Gross, RW