Cholesterol attenuates the membrane perturbing properties of beta-amyloid peptides.

Growing evidence indicates a significant linkage between Abeta and cholesterol metabolism, although the exact role of cholesterol in brain aging and in the pathogenesis of AD is still unknown. Recently, in vitro and in vivo modification of cell cholesterol and its effect on Abeta-generation became a straight focus in the research of AD. In the present study, we discretely modulated the cholesterol contents of neuronal membranes from mice of different ages in vivo and in vitro using lovastatin and methyl-beta-cyclodextrin, respectively. The aim of the study was to investigate whether this modulation results in altered physico-chemical membrane properties. Therefore, we performed membrane fluidity measurements using three fluorescent dyes labeling different membrane regions. Furthermore, we evaluated the effects of cholesterol modulation on the membrane disturbing properties of Abeta. Modulation of membrane cholesterol content in vivo and in vitro was linked to changes in membrane properties. Very interestingly, cholesterol content of in vitro modulated neuronal membranes was negatively correlated with the membrane perturbing effects of Abeta.