From brain to food: Analysis of phosphatidylcholins, lyso-phosphatidylcholins and phosphatidylcholin plasmalogens derivates in Alzheimer's disease human post mortem brains and mice model via mass spectrometry

From brain to food: Analysis of phosphatidylcholins, lyso-phosphatidylcholins and phosphatidylcholin plasmalogens derivates in Alzheimer's disease human post mortem brains and mice model via mass spectrometry
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DOI:
10.1016/j.chroma.2011.07.073
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发表时间:
2011-10-21
影响因子:
4.1
通讯作者:
Hartmann, Tobias
Hartmann, Tobias
中科院分区:
化学2区
文献类型:
--
作者:
Grimm, Marcus O. W.;Groesgen, Sven;Hartmann, Tobias

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阿尔茨海默病(AD)是一种毁灭性的神经退行性疾病,其特征是细胞外老年斑,主要由40-42个氨基酸组成的长肽AP和细胞内神经纤维缠结,并伴有过度的突触丢失。近年来,越来越多的证据表明营养,尤其是多不饱和脂肪酸影响AD的发病。特别是中年饮食习惯与特定的脂肪酸(FA)的消费似乎影响疾病的风险。食物摄入和疾病之间的及时分离使得对饮食习惯的详细分析和准确的食物分析几乎无法实现直接关联。绕过这些困难的一个可能的解决方案是研究人死后脑中FA的组成。本研究对AD患者脑内主要磷脂磷脂酰胆碱(PC)、磷脂酰胆碱-纤溶酶原(PC-PL)和溶血磷脂酰胆碱(Lyso-PC)进行了研究。用AB Sciex 4000QTrap质谱仪分析了30只AD(平均78岁)和14只年龄匹配的对照小鼠(平均77.4岁)和APP转基因小鼠的额叶皮质、颞叶皮质和小脑。分析了PC、PC-PL和LYSO-PC代谢产物的饱和程度和FA组成。正如预期的那样,大多数脂质物种没有表现出显著的差异,但有趣的是,少数几种脂质物种显示出AD大脑中非常显著的减少。这些脂肪酸是关于AD病理的进一步食品分析的潜在候选者。此外,我们还发现,本研究所采用的多反应监测方法适用于微量(10亩L)脑组织的半定量分析。(C)2011年爱思唯尔BM。版权所有。
Alzheimer's disease (AD) is a devastating neurodegenerative disorder characterized by extracellular senile plaques mainly consisting of AP, a 40-42 amino acid long peptide, and intracellular neurofibrillary tangles, accompanied by an excessive loss of synapses. Recently evidence accumulated that nutrition, especially polyunsaturated fatty acids, influences AD pathogenesis. Especially mid-life food habits with the consumption of specific fatty acids (FA) appear to influence the disease risk. The timely separation between food intake and disease makes a direct correlation with detailed analysis of eating habits combined with accurate food analysis nearly unattainable. A possible solution to circumvent these difficulties is to investigate the FA composition in human post mortem brain. In this study we focused on the main phospholipids phosphatidylcholin (PC), phosphatidylcholin-plasmalogen (PC-PL) and lysophosphatidylcholin (lyso-PC) in AD brains compared to control brains. Frontal cortices, temporal cortices and cerebellum of 30 AD (mean 78 years) and 14 control aged matched brains (mean 77.4 years) as well as APP transgenic mice compared to control mice were analyzed using an AB Sciex 4000 Qtrap mass spectrometer utilizing a FIA MS/MS method. PC, PC-PL and lyso-PC metabolites were analyzed in respect to saturation level and FA composition. As expected, the majority of the lipid species showed no significant differences, but interestingly a few species revealed a highly significant reduction in AD brains. These FAs are potential candidates for further food analysis in respect to AD pathology. Additionally, we show that the method applied with multiple reaction monitoring (MRM) used for this study is suitable for semi quantitative analysis of small amounts (10 mu l) of brain tissue. (C) 2011 Elsevier BM. All rights reserved.