Disturbed choline plasmalogen and phospholipid fatty acid concentrations in Alzheimer's disease prefrontal cortex.
Disturbed choline plasmalogen and phospholipid fatty acid concentrations in Alzheimer's disease prefrontal cortex.
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DOI：
10.3233/jad-2011-101608
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发表时间：
2011
期刊：
影响因子：
--
通讯作者：
Rao JS
中科院分区：
文献类型：
--
作者：
Igarashi M;Ma K;Gao F;Kim HW;Rapoport SI;Rao JS
阿尔茨海默病(AD)是一种进行性神经退行性疾病，其特征是脑内沉积含有β-淀粉样蛋白、神经纤维缠结、突触丢失、神经炎症和花生四烯酸(AA，20：4N-6)代谢酶过度表达的老年性(神经炎)斑块。据报道，脂质浓度在不同的大脑区域发生了变化，但通常是部分和/或占总浓度的百分比。在这项研究中，我们测量了10名AD患者和9名对照组死后前额叶皮质(Brodmann区9区)各种脂质的绝对浓度(每克湿重)。阿尔茨海默病患者和对照组的平均脑脂、磷脂、胆固醇和甘油三酯浓度没有显著差异。纤溶酶原胆碱显著减少了73%，但其他磷脂没有变化。总磷脂中的脂肪酸浓度与对照没有差异。而二十二碳六烯酸(DHA，22：6N-3)在乙醇胺甘油磷脂和胆碱甘油磷脂中减少，而在磷脂酰肌醇中增加。胆碱甘油磷脂中AA减少，而磷脂酰肌醇中AA增加，而AA延伸产物二十二碳四烯酸(22：4N-6)减少总脑脂、胆固醇酯和甘油三酯。这些脂质改变可能导致AD的细胞膜不稳定和突触丢失，反映了神经炎症和兴奋性毒性。
Alzheimer disease (AD) is a progressive neurodegenerative disorder characterized by brain deposition of senile (neuritic) plaques containing β-amyloid, neurofibrillary tangles, synaptic loss, neuroinflammation, and overexpression of arachidonic acid (AA, 20:4n-6) metabolizing enzymes. Lipid concentration changes have been reported in different brain regions, but often partially and/or as a percent of the total concentration. In this study, we measured absolute concentrations (per gram wet weight) of a wide range of lipids in postmortem prefrontal cortex (Brodmann area 9) from 10 AD patients and 9 controls. Mean total brain lipid, phospholipid, cholesterol and triglyceride concentrations did not differ significantly between AD and controls. There was a significant 73% decrease in plasmalogen choline, but no difference in other measured phospholipids. Fatty acid concentrations in total phospholipid did not differ from control. However, docosahexaenoic acid (DHA, 22:6n-3) was reduced in ethanolamine glycerophospholipid and choline glycerophospholipid, but increased in phosphatidylinositol. AA was reduced in choline glycerophospholipid, but increased in phosphatidylinositol, while docosatetraenoic acid (22:4n-6), an AA elongation product, was reduced in total brain lipid, cholesteryl ester and triglyceride. These lipid changes may contribute to membrane instability and synaptic loss in AD, and reflect neuroinflammation and excitotoxicity.