Schönknecht Peter, Lütjohann Dieter, Pantel Johannes, Bardenheuer Habertus, Hartmann Tobias, von Bergmann Klaus, Beyreuther Konrad, Schröder Johannes
Section of Geriatric Psychiatry, Department of Psychiatry, University of Heidelberg, Voss-Strasse 4, 69115, Germany.
Neurosci Lett. 2002 May 10;324(1):83-5. doi: 10.1016/s0304-3940(02)00164-7.
Experiments in cell cultures indicate that accumulation of cholesterol in hippocampal neurons results in an accelerated cleavage of amyloid precursor protein into amyloidogenic components. To be eliminated from the brain, cholesterol is converted to 24S-hydroxycholesterol which may reflect cerebral cholesterol turnover. We investigated cerebrospinal fluid (CSF) concentrations of 24S-hydroxycholesterol in a group of 14 Alzheimer's disease (AD) patients and ten healthy controls without any cognitive deficits or psychiatric or neurological disorders. To exclude potential effects of circulating plasma cholesterol on CSF 24S-hydroxycholesterol levels, only patients and controls with cholesterol levels in the normal range of 150-230 mg/dl were included. We found significantly elevated 24S-hydroxycholesterol CSF but not plasma levels in AD patients compared with healthy controls. Our results demonstrate that CSF 24S-hydroxycholesterol is increased in AD. This effect does not seem to be triggered by plasma cholesterol levels since the latter did not significantly differ between groups.
细胞培养实验表明，海马神经元中胆固醇的积累会导致淀粉样前体蛋白加速裂解为淀粉样生成成分。为了从大脑中清除，胆固醇会转化为24S-羟基胆固醇，这可能反映了脑内胆固醇的周转情况。我们调查了一组14名阿尔茨海默病（AD）患者和10名无任何认知缺陷、精神或神经疾病的健康对照者脑脊液（CSF）中24S-羟基胆固醇的浓度。为排除循环血浆胆固醇对CSF中24S-羟基胆固醇水平的潜在影响，仅纳入胆固醇水平在150-230mg/dl正常范围内的患者和对照者。我们发现，与健康对照者相比，AD患者CSF中24S-羟基胆固醇水平显著升高，但血浆水平未升高。我们的结果表明，AD患者CSF中24S-羟基胆固醇升高。由于各组间血浆胆固醇水平无显著差异，这种效应似乎不是由血浆胆固醇水平触发的。
