Shafaati Marjan, Solomon Alina, Kivipelto Miia, Björkhem Ingemar, Leoni Valerio
Department of Laboratory Medicine, Division of Clinical Chemistry, Karolinska Institutet, Karolinska University Hospital, Huddinge, Stockholm, Sweden.
Neurosci Lett. 2007 Sep 25;425(2):78-82. doi: 10.1016/j.neulet.2007.08.014. Epub 2007 Aug 15.
Evidence was recently presented from in vitro studies that 24S-hydroxycholesterol acts as a signalling molecule inducing apoE-mediated cholesterol efflux from astrocytoma cells, and that there is a direct effect of the oxysterol on apoE transcription, protein synthesis and secretion. Consistent with this mechanism, a significant correlation is demonstrated here between levels of apoE and 24S-hydroxycholesterol in cerebrospinal fluid from patients with Alzheimer's disease and patients with mild cognitive impairment. Such a correlation was not found in control patients. There was no correlation between levels of apoE and cholesterol in cerebrospinal fluid from controls. The results are consistent with a close coupling between release of 24S-hydroxycholesterol and apoE secretion under conditions with neuronal degeneration. The levels of apoE in cerebrospinal fluid were also correlated to the levels of Tau and the possibility is discussed that the level of apoE in cerebrospinal fluid may be used as a marker of neurodegeneration.
最近的体外研究证据表明，24S-羟基胆固醇作为一种信号分子，可诱导载脂蛋白E（apoE）介导的星形细胞瘤细胞胆固醇外流，并且该氧化固醇对apoE转录、蛋白质合成和分泌有直接影响。与此机制一致，本研究证明，阿尔茨海默病患者和轻度认知障碍患者脑脊液中apoE水平与24S-羟基胆固醇水平之间存在显著相关性。在对照患者中未发现这种相关性。对照者脑脊液中apoE水平与胆固醇水平之间无相关性。这些结果与神经元变性条件下24S-羟基胆固醇释放与apoE分泌紧密相关一致。脑脊液中apoE水平也与Tau水平相关，并讨论了脑脊液中apoE水平可能用作神经变性标志物的可能性。
