Statins have been reported to lower the risk of developing Alzheimer's disease; however, the mechanism of this potentially important neuroprotective action is not understood. Lowering cholesterol levels does not appear to be the primary mechanism. Statins have pleiotropic effects in addition to lowering cholesterol, and statins may act on several different pathways involving distinct gene expression patterns that would be difficult to determine by focusing on a few genes or their products in a single study. In addition, gene expression patterns may be specific to a particular statin. To understand the molecular targets of statins in brain, DNA microarrays were used to identify gene expression patterns in the cerebral cortex of mice chronically treated with lovastatin, pravastatin, and simvastatin. Furthermore, brain statin levels were determined using liquid chromatography/tandem mass spectrometry. These studies revealed 15 genes involved in cell growth and signaling and trafficking that were similarly changed by all three statins. Overall, simvastatin had the greatest influence on expression as demonstrated by its ability to modify the expression of 23 genes in addition to those changed by all three drugs. Of particular interest was the expression of genes associated with apoptotic pathways that were altered by simvastatin. Reverse transcription-polymerase chain reaction experiments confirmed the microarray findings. All three drugs were detected in the cerebral cortex, and acute experiments revealed that statins are relatively rapidly removed from the brain. These results provide new insight into possible mechanisms for the potential efficacy of statins in reducing the risk of Alzheimer's disease and lay the foundation for future studies.

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BackgroundObjective of the study was to evaluate the diagnostic value of novel ultrasonographic modalities in comparison with simultaneously performed liver biopsy.MethodsThe results of simultaneously performed examinations using Acoustic Structure Quantification (ASQ), Virtual Touch Imaging and Quantification (VTIQ) and Virtual Touch Tissue Quantification (VTTQ) were compared with the findings of liver biopsy in patients with a wide variety of diffuse hepatopathies (n = 51). The histologically determined fibrosis stage according to Desmet and Scheuer was compared with quantitative measurements returned by the ultrasonographic imaging modalities.ResultsNo statistically significant correlation with histologically determined fibrosis stage could be identified for any measurements returned using ASQ. Increasing severity of hepatic steatosis, however, was associated with a reduction in the focal disturbance (FD) ratio (r = −0.55; p < 0.0001). The shearwave velocities measured using VTTQ satisfyingly correlated with fibrosis stage (r = 0.56; p > 0.0001). Fibrosis stages > F2 were associated with an area under the curve (AUC) of 0.94 (95 %-CI:0.84–0.99). A cut-off value for shearwave velocity of 1.66 m/s was determined with a sensitivity of 100 % and a specificity of 84 %. VTIQ showed a less pronounced but acceptable correlation with fibrosis stage (r = 0.35; p = 0.0154). For fibrosis stages > F2 analysis showed an AUC of 0.84 (95 %-CI:0.70–0.93). The cut-off value was 1.82 m/s with a sensitivity of 100 % and a specificity of 58 %.ConclusionWhile ASQ showed no diagnostic advantage in our patient collective, VTTQ showed high reliability for determining severe liver fibrosis in a group of patients with diffuse liver diseases of different etiology.