Cholesterol protects PC12 cells from beta-amyloid induced calcium disordering and cytotoxicity.

THE neurotoxic action of beta-amyloid seems to play an important role in the pathogenesis of Alzheimer's disease. The disruption of calcium homeostasis by beta-amyloid has been suspected to be the mechanism of its neurotoxicity. We found that beta-amyloid 25-35 induces a rapid increase in cytosolic calcium of PC12 cells, and subsequently, a dramatic decrease in cell viability. The increase in cytosolic calcium induced by beta-amyloid is effectively blocked by cholesterol in a dose-dependent manner. Furthermore, pretreatment of PC12 cells with cholesterol also significantly attenuates the neurotoxicity induced by beta-amyloid. These findings suggest that extracellular free cholesterol can protect neurones from beta-amyloid neurotoxicity mediated by the disruption of calcium homeostasis.