Journal article

Publication year: 2013

Pages: 590-594

Journal: Pharmazie

Volume number: 68

Issue number: 7

ISSN: 0031-7144

DOI Link: https://doi.org/10.1691/ph.2013.6529

Publisher: Govi Verlag GMBH

Abstract: 
Statins (HMG-CoA reductase or CSE-inhibitors) strongly reduce the cellular amyloid-beta protein production by modulating the processing of amyloid precursor protein (APP) in vitro. Several in vivo studies have addressed this important issue in transgenic mouse models with inconsistent results. Recently, we showed that simvastatin alters cholesterol distribution in synaptosomal membranes (SPM) in vivo. In the present study, we tested whether these changes in cholesterol membrane distribution affect APP-processing in vivo. Female APP751(SL) mice were force-fed with simvastatin (50 mg/kg b.wt.) by oral gavage over a time period of 3 weeks. Our data show that chronic simvastatin treatment decreased cholesterol levels in the brain and affected cholesterol distribution within SPM. Simvastatin significantly increased the levels of insoluble A beta(1-40) and A beta(1-42) but reduced levels of soluble A beta(1-40) in the brain. The reduction of soluble A beta(1-40) levels in the brain was associated with an increase of Plasma-levels of A beta(1-40) in simvastatin-treated animals that may indicate enhanced A beta(1-40)-clearance from the brain. Although the observed alteration in transbilayer cholesterol is likely to be involved in changes of APP processing by alpha-, beta- and gamma-secretase, we cannot exclude other potential mechanisms of statins such as lipid and non-lipid related, pleiotropic effects. Our data were evaluated in reference to published studies and a possible gender effect was identified.

Harvard Citation style: Eckert, G., Reik, C. and Müller, W. (2013) Simvastatin alters membrane cholesterol distribution and beta-amyloid levels in brains of female APP751(SL) mice, Pharmazie, 68(7), pp. 590-594. https://doi.org/10.1691/ph.2013.6529

APA Citation style: Eckert, G., Reik, C., & Müller, W. (2013). Simvastatin alters membrane cholesterol distribution and beta-amyloid levels in brains of female APP751(SL) mice. Pharmazie. 68(7), 590-594. https://doi.org/10.1691/ph.2013.6529