EVIDENCE FOR A MEMBRANE DEFECT IN ALZHEIMER-DISEASE BRAIN
EVIDENCE FOR A MEMBRANE DEFECT IN ALZHEIMER-DISEASE BRAIN
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DOI：
10.1073/pnas.89.5.1671
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发表时间：
1992-03-01
影响因子：
11.1
通讯作者：
WURTMAN, RJ
中科院分区：
文献类型：
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作者：
NITSCH, RM;BLUSZTAJN, JK;WURTMAN, RJ
为了确定阿尔茨海默病大脑中的神经退行性变是否与结构细胞膜分子的降解有关，我们测量了阿尔茨海默病患者和匹配对照死后大脑的三个皮质区域中主要膜磷脂及其代谢物的组织水平。磷脂中，磷脂酰胆碱和磷脂酰乙醇胺显着降低（P < 0.05）。初始磷脂前体胆碱和乙醇胺显着减少（P < 0.05），而磷脂脱酰产物甘油磷酸胆碱则增加。在所有检查的阿尔茨海默病大脑区域中，甘油磷酸胆碱与胆碱以及甘油磷酸乙醇胺与乙醇胺的比率均显着增加。阿尔茨海默病脑中甘油磷酸胆碱降解酶甘油磷酸胆碱磷酸二酯酶的活性正常。磷脂的减少和磷脂分解代谢物的增加之间存在接近化学计量的关系。这些数据与阿尔茨海默病大脑中膜磷脂降解增加一致。在亨廷顿病、帕金森病或唐氏综合症患者的大脑中没有检测到类似的磷脂异常。我们的结论是，这里描述的磷脂异常不是神经退行性变的附带现象，它们可能是阿尔茨海默病的病理机制所特有的。
To determine whether neurodegeneration in Alzheimer disease brain is associated with degradation of structural cell membrane molecules, we measured tissue levels of the major membrane phospholipids and their metabolites in three cortical areas from postmortem brains of Alzheimer disease patients and matched controls. Among phospholipids, there was a significant (P < 0.05) decrease in phosphatidylcholine and phosphatidylethanolamine. There were significant (P < 0.05) decreases in the initial phospholipid precursors choline and ethanolamine and increases in the phospholipid deacylation product glycerophosphocholine. The ratios of glycerophosphocholine to choline and glycerophosphoethanolamine to ethanolamine were significantly increased in all examined Alzheimer disease brain regions. The activity of the glycerophosphocholine-degrading enzyme glycerophosphocholine cholinephosphodiesterase was normal in Alzheimer disease brain. There was a near stoichiometric relationship between the decrease in phospholipids and the increase of phospholipid catabolites. These data are consistent with increased membrane phospholipid degradation in Alzheimer disease brain. Similar phospholipid abnormalities were not detected in brains of patients with Huntington disease, Parkinson disease, or Down syndrome. We conclude that the phospholipid abnormalities described here are not an epiphenomenon of neurodegeneration and that they may be specific for the pathomechanism of Alzheimer disease.