Cholesterol potentiates β-amyloid-induced toxicity in human neuroblastoma cells:: Involvement of oxidative stress

Alterations in brain cholesterol concentration and metabolism seem to be involved in Alzheimer's disease (AD). In fact, several experimental studies have reported that modification of cholesterol content can influence the expression of the amyloid precursor protein (APP) and amyloid beta peptide (A beta) production. However, it remains to be determined if changes in neuronal cholesterol content may influence the toxicity of A beta peptides and the mechanism involved. Aged mice, AD patients and neurons exposed to A beta, show a significant increase in membrane-associated oxidative stress. Since A beta is able to promote oxidative stress directly by catalytically producing H2O2 from cholesterol, the present work analyzed the effect of high cholesterol incorporated into human neuroblastoma cells in A beta-mediated neurotoxicity and the role of reactive oxygen species (ROS) generation. Neuronal viability was studied also in the presence of 24S-hydroxycholesterol, the main cholesterol metabolite in brain, as well as the potential protective role of the lipophilic statin, lovastatin.