Department of Psychiatry, University Hospital of Lausanne, Lausanne, Switzerland.
J Neurochem. 2012 Oct;123(2):310-6. doi: 10.1111/j.1471-4159.2012.07893.x. Epub 2012 Aug 23.
Disturbances of the cholesterol metabolism are associated with Alzheimer's disease (AD) risk and related cerebral pathology. Experimental studies found changing levels of cholesterol and its metabolites 24S-hydroxycholesterol (24S-OHC) and 27-hydroxycholesterol (27-OHC) to contribute to amyloidogenesis by increasing the production of soluble amyloid precursor protein (sAPP). The aim of this study was to evaluate the relationship between the CSF and circulating cholesterol 24S-OHC and 27-OHC, and the sAPP production as measured by CSF concentrations of sAPP forms in humans. The plasma and the CSF concentrations of cholesterol, 24S-OHC and 27-OHC, and the CSF concentrations of sAPPα, sAPPβ, and Aß1-42 were assessed in subjects with AD and controls with normal cognition. In multivariate regression tests including age, gender, albumin ratio, and apolipoprotein E (APOE)ε4 status CSF cholesterol, 24S-OHC, and 27-OHC independently predicted the concentrations of sAPPα and sAPPβ. The associations remained significant when analyses were separately performed in the AD group. Furthermore, plasma 27-OHC concentrations were associated with the CSF sAPP levels. The results suggest that high CSF concentrations of cholesterol, 24S-OHC, and 27-OHC are associated with increased production of both sAPP forms in AD.
胆固醇代谢紊乱与阿尔茨海默病（AD）风险和相关的脑病理学有关。实验研究发现，胆固醇及其代谢物 24S-羟胆固醇（24S-OHC）和 27-羟胆固醇（27-OHC）水平的变化通过增加可溶性淀粉样前体蛋白（sAPP）的产生而有助于淀粉样蛋白形成。本研究旨在评估 CSF 和循环胆固醇 24S-OHC 和 27-OHC 与 sAPP 产生之间的关系，sAPP 产生通过 CSF 中 sAPP 形式的浓度来衡量。评估了 AD 患者和认知正常对照者的血浆和 CSF 胆固醇、24S-OHC 和 27-OHC 浓度以及 CSF sAPPα、sAPPβ 和 Aβ1-42 浓度。在包括年龄、性别、白蛋白比值和载脂蛋白 E（APOE）ε4 状态在内的多元回归测试中，CSF 胆固醇、24S-OHC 和 27-OHC 独立预测了 sAPPα和 sAPPβ的浓度。当分别在 AD 组中进行分析时，相关性仍然显著。此外，血浆 27-OHC 浓度与 CSF sAPP 水平相关。结果表明，AD 患者 CSF 中胆固醇、24S-OHC 和 27-OHC 浓度升高与两种 sAPP 形式的产生增加有关。
