Kölsch Heike, Heun Reinhard, Jessen Frank, Popp Julius, Hentschel Frank, Maier Wolfgang, Lütjohann Dieter
Department of Psychiatry, University of Bonn, 53105 Bonn, Germany.
Biochim Biophys Acta. 2010 Aug;1801(8):945-50. doi: 10.1016/j.bbalip.2010.03.001. Epub 2010 Mar 11.
Cerebral and extracerebral cholesterol metabolism are altered in Alzheimer's disease (AD) as indicated by reduced plasma levels of the cholesterol elimination products 24S-hydroxycholesterol, which is of cerebral origin, and of 27-hydroxycholesterol, which is formed extracerebrally. However, it has to be evaluated, if changes of cholesterol metabolism in the whole body or in the CNS are exclusively due to the altered elimination of cholesterol or are also due to altered de novo synthesis in AD. We investigated CSF and plasma levels of cholesterol and of its precursors lanosterol, lathosterol and desmosterol in AD patients and non-demented controls. We found CSF levels of cholesterol (p=0.011), absolute levels of all investigated cholesterol precursors (each p<0.001) and ratios of cholesterol precursors/cholesterol (each <0.01) to be lower in AD patients as compared to controls. In plasma, the absolute levels of lanosterol (p=0.026) and lathosterol (p<0.001) and the ratio of lathosterol/cholesterol (p=0.002) but none of the other investigated parameters were reduced in AD patients (p>0.1). Furthermore, ratios of desmosterol/lathosterol in CSF (p=0.023) and plasma (p=0.009) were higher in AD patients as compared to controls. Our data support the hypothesis that cholesterol metabolism is altered in AD and further suggest that especially cholesterol de novo synthesis within the CNS of AD patients might be reduced. These findings raise doubt on a beneficial effect of cholesterol lowering treatment in manifest AD.
阿尔茨海默病（AD）患者的脑内和脑外胆固醇代谢均发生改变，这表现为胆固醇清除产物血浆水平降低，其中脑源性的24S-羟基胆固醇和脑外生成的27-羟基胆固醇水平均降低。然而，必须评估全身或中枢神经系统胆固醇代谢的变化是仅仅由于胆固醇清除改变所致，还是也归因于AD中从头合成的改变。我们研究了AD患者和非痴呆对照者脑脊液（CSF）和血浆中胆固醇及其前体羊毛甾醇、胆甾烯醇和 desmosterol 的水平。我们发现，与对照组相比，AD患者的CSF胆固醇水平（p = 0.011）、所有研究的胆固醇前体的绝对水平（各p < 0.001）以及胆固醇前体/胆固醇的比率（各<0.01）均较低。在血浆中，AD患者的羊毛甾醇绝对水平（p = 0.026）和胆甾烯醇绝对水平（p < 0.001）以及胆甾烯醇/胆固醇比率（p = 0.002）降低，但其他研究参数均未降低（p>0.1）。此外，与对照组相比，AD患者CSF（p = 0.023）和血浆（p = 0.009）中desmosterol/胆甾烯醇的比率更高。我们的数据支持AD中胆固醇代谢发生改变的假说，并进一步表明，尤其是AD患者中枢神经系统内的胆固醇从头合成可能减少。这些发现对在显性AD中进行降胆固醇治疗的有益效果提出了质疑。
