tcome as the previous AVE8062A studies have shown that APOE e4 allele increases Ab deposition in the cerebral cortex of AD brain as well as in cognitively normal aging brain. It has been shown that APOE e4 allele is associated with reduced levels of Ab42 in the CSF, which is considered to reflect increased Ab42 levels in the brain. Furthermore, a recent study showed that ApoE4 is less efficient in Ab clearance than ApoE3 in a mouse model expressing human ApoE isoforms. Previous studies have assessed the ApoE protein levels in post-mortem brain samples with contrasting results, but this may partly be due to the different brain regions used in the assessments. Only a few studies have elucidated APOE mRNA levels in the post-mortem brain samples. In the present study, APOE mRNA levels showed an increasing trend among the AD patients homozygous for APOE e4 as compared to patients heterozygous for APOE e4 or with no e4 allele. This finding is in agreement with a previous study showing that APOE mRNA 16707462 levels are increased in the temporal lobe of AD patients carrying the APOE e4 allele. Effects of NR1H3 Gene Variation on LXRa and AD the temporal cortex of patients with CC genotype as compared to the TT genotype. NR1H3 genotype does not affect b-secretase activity in the temporal cortex. Ab42 levels in the CSF are not significantly changed with respect to the rs7120118 genotype. Mean values are indicated in the graphs. doi:10.1371/journal.pone.0080700.g004 Taken together, our data suggest that APOE e4 allele increases the soluble Ab42 levels in the brain tissue in a dose-dependent manner, but does not significantly affect the expression of APOE. Previously, gender-, age-, and APOE-adjusted logistic regression analysis revealed a protective effect for the 15722457 C allele carriers of rs7120118 among a Finnish clinic-based AD-control cohort, indicating that these patients have a decreased risk for AD. Consistent with this finding, the CC genotype of rs7120118 was found to be underrepresented in the severe group in the present study. This result, however, did not reach statistical significance. Moreover, there were proportionally more subjects with the CC genotype in the moderate group as compared to the mild group, arguing against an additive effect for the C allele in this sample set. Nevertheless, the protective effect of the C allele of rs7120118 was supported by the biochemical measurements showing significantly decreased soluble Ab42 levels in the brain of AD patients with rs7120118 CC genotype as compared to the TT genotype. bsecretase activity was not affected by the rs7120118 variation, suggesting that the decrease in the soluble levels of Ab42 may be linked to increased clearance and/or degradation rather than decreased production of Ab. This is a plausible assumption considering that the LXRa agonists increase the clearance of Ab. The Ab42 levels in the CSF did not show significant alteration with respect to the rs7120118 genotypes, but this could be due to the small number of CSF samples available for the present analysis. Since the mRNA levels of NR1H3, ABCA1, ABCG1, and APOE did 
not change with respect to the severity of AD, we were able to address the question whether the rs7120118 variation affects the mRNA levels of these genes. Consequently, the mRNA levels of NR1H3 were found to be significantly increased among the AD patients with the rs7120118 CT genotype as compared to the TT genotype. However, since the mRNA levels of NR1H3 in the subjects wit