Sauder S, Kölsch H, Lütjohann D, Schulz A, von Bergmann K, Maier W, Heun R
Department of Psychiatry, University of Bonn, Germany.
J Neural Transm (Vienna). 2005 Oct;112(10):1381-9. doi: 10.1007/s00702-004-0267-z. Epub 2005 Jan 24.
The peroxisome proliferator-activated receptor gamma (PPARgamma) is a nuclear hormone receptor, that is involved in lipid and glucose metabolism, which both seem to influence the risk of Alzheimer's disease (AD). 24S-Hydroxycholesterol is the major cholesterol elimination product of the brain and plasma and CSF 24S-hydroxycholesterol levels are altered in patients with neurodegenerative diseases. We investigated the effect of the common Pro12Ala variant of the PPARgamma gene on plasma cholesterol levels and 24S-hydroxycholesterol/ cholesterol ratios in 124 AD patients and 77 healthy controls. Furthermore, the influence of PPARgamma polymorphism on the risk of AD in 247 AD patients and 324 healthy controls was investigated. We found that PPARgamma Pro12Ala polymorphism influenced plasma 24S-hydroxycholesterol/ cholesterol ratios in AD patients in that carriers of the Ala allele presented with higher ratios than homozygote carriers of the Pro-allele. PPARgamma polymorphism did not influence the risk of AD. These results might point to an influence of PPARgamma Pro12Ala polymorphism on the elimination of 24S-hydroxycholesterol.
过氧化物酶体增殖物激活受体γ（PPARγ）是一种核激素受体，参与脂质和葡萄糖代谢，而这两者似乎都影响阿尔茨海默病（AD）的发病风险。24S-羟基胆固醇是大脑、血浆中胆固醇的主要清除产物，神经退行性疾病患者血浆和脑脊液中的24S-羟基胆固醇水平会发生改变。我们研究了PPARγ基因常见的Pro12Ala变异对124例AD患者和77例健康对照者血浆胆固醇水平以及24S-羟基胆固醇/胆固醇比值的影响。此外，还研究了PPARγ基因多态性对247例AD患者和324例健康对照者患AD风险的影响。我们发现，PPARγ Pro12Ala多态性影响AD患者血浆24S-羟基胆固醇/胆固醇比值，即Ala等位基因携带者的该比值高于Pro等位基因纯合子携带者。PPARγ基因多态性不影响AD发病风险。这些结果可能表明PPARγ Pro12Ala多态性对24S-羟基胆固醇的清除有影响。
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