Walter Anna, Korth Ulrike, Hilgert Michael, Hartmann Joachim, Weichel Oksana, Hilgert Marion, Fassbender Klaus, Schmitt Andrea, Klein Jochen
Department of Pharmacology, Johannes Gutenberg University of Mainz, Mainz 55101, Germany.
Neurobiol Aging. 2004 Nov-Dec;25(10):1299-303. doi: 10.1016/j.neurobiolaging.2004.02.016.
Experimental and clinical studies give evidence for breakdown of membrane phospholipids during neurodegeneration. In the present study, we measured the levels of glycerophosphocholine (GPCh), phosphocholine (PCh), and choline, that is, water-soluble metabolites of phosphatidylcholine (PtdCho), in human cerebrospinal fluid (CSF). Among 30 cognitively normal patients the average CSF levels of GPCh, phosphocholine and choline were 3.64, 1.28, and 1.93 microM, respectively; metabolite levels did not change with increasing age. When compared with age-matched controls, patients with Alzheimer's disease had elevated levels of all choline metabolites: GPCh was significantly increased by 76% (P<0.01), phosphocholine by 52% (P<0.05), and free choline (Ch) by 39%. Six patients with vascular dementia had lower choline and elevated phosphocholine levels, when compared to controls, but normal levels of GPCh. These data demonstrate that Alzheimer's disease is accompanied by an increased PtdCho hydrolysis in the brain. PtdCho breakdown seems to be mediated by phospholipase A2 and leads to significantly elevated levels of GPCh in CSF.
实验和临床研究为神经退行性变过程中膜磷脂的分解提供了证据。在本研究中，我们测量了人脑脊液（CSF）中甘油磷酸胆碱（GPCh）、磷酸胆碱（PCh）和胆碱（即磷脂酰胆碱（PtdCho）的水溶性代谢产物）的水平。在30名认知正常的患者中，GPCh、磷酸胆碱和胆碱的脑脊液平均水平分别为3.64、1.28和1.93微摩尔；代谢产物水平不会随年龄增长而变化。与年龄匹配的对照组相比，阿尔茨海默病患者所有胆碱代谢产物的水平均升高：GPCh显著增加76%（P<0.01），磷酸胆碱增加52%（P<0.05），游离胆碱（Ch）增加39%。与对照组相比，6名血管性痴呆患者的胆碱水平较低，磷酸胆碱水平升高，但GPCh水平正常。这些数据表明，阿尔茨海默病伴有大脑中PtdCho水解增加。PtdCho分解似乎由磷脂酶A2介导，并导致脑脊液中GPCh水平显著升高。
