PPARD haplotype influences cholesterol metabolism but is no risk factor of Alzheimer's disease

Cholesterol metabolism is involved in Alzheimer's disease (AD) pathogenesis: increased cholesterol blood levels are detected in AD patients, and treatment with statins reduces the risk of AD. The peroxisome proliferator-activated receptor delta protein (PPARdelta), is a member of the steroid hormone super family of ligand-inducible transcription factors, and is of major relevance in lipid and cholesterol metabolism. We investigated three frequent polymorphisms located in exons 4 (rs2016520) and 9 (rs3734254 and rs9794) of the PPARdelta gene (PPARD) for their putative influence on the risk of AD and on plasma levels of cholesterol, 24S-hydroxycholesterol and 27-hydroxycholesterol. The study population consisted of 167 AD patients (mean age: 74.27+/-9.37 years; female 78.6%) and 194 controls (mean age: 73.26+/-8.37 years; female 57.2%). Haplotype analysis was perfomed, however, we did not find PPARD haplotypes to influence the risk of AD. In contrast to these results, a two marker haplotype consisting of rs2016520 and rs9794 in AD patients showed a significant effect on the relative plasma levels of 24S-hydroxycholesterol (carriers: 32.1+/-2.8ng/mg; non-carriers: 40.3+/-1.4ng/mg; p=0.016) and 27-hydroxycholesterol (carriers: 40.8+/-7.7ng/mg; non-carriers: 58.6+/-2.3ng/mg; p=0.002) but not in non-demented controls. Our results suggest that PPARD haplotypes might influence levels of cholesterol metabolites in AD patients, but act not as risk factors of AD.