Hypercholesterolemia, a major risk factor for age related diseases such as atherosclerosis and Alzheimer's disease (AD). Changes in human plasma cholesterol levels results from the interaction between multiple genetic and environmental factors. The accumulation of excess cholesterol in blood vessels leads to atherosclerosis. Studies show that differential expression of oxidative stress proteins, lipid metabolism related enzymes and receptors response to atherogenic diet. Excess brain cholesterol has been associated with increased formation and deposition of amyloid-b peptide from amyloid precursor protein which may contribute to the risk and pathogenesis of AD. More than 50 genes have been reported to influence the risk of late-onset AD. Several of these genes might be important in cholesterol metabolism and transport.

On the basis of these results, an in vivo study has been carried out. Rabbits were fed with cholesterol supplemented diet or cholesterol supplemented diet plus alpha tocopherol, after 4 weeks aortas and brains were removed. Proteasome function, protein carbonylation, tau hyperphoshorylation and amyloid-bprotein evaluated in the brain of hypercholestrolemic rabbits. The results indicate a cellular mechanism for hypercholesterolemia induced AD similar changes will be discussed.