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Influence of peroxisome proliferator-activated receptor γ gene polymorphism on 24S-hydroxycholesterol levels in Alzheimer’s patients

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Summary.

The peroxisome proliferator-activated receptor γ (PPARγ) 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 PPARγ gene on plasma cholesterol levels and 24S-hydroxycholesterol/ cholesterol ratios in 124 AD patients and 77 healthy controls. Furthermore, the influence of PPARγ polymorphism on the risk of AD in 247 AD patients and 324 healthy controls was investigated. We found that PPARγ 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. PPARγ polymorphism did not influence the risk of AD. These results might point to an influence of PPARγ Pro12Ala polymorphism on the elimination of 24S-hydroxycholesterol.

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Sauder, S., Kölsch, H., Lütjohann, D. et al. Influence of peroxisome proliferator-activated receptor γ gene polymorphism on 24S-hydroxycholesterol levels in Alzheimer’s patients. J Neural Transm 112, 1381–1389 (2005). https://doi.org/10.1007/s00702-004-0267-z

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