Cholesterol and Alzheimer's disease - Is there a link?

The A beta -amyloid peptide (A beta), the main component of amyloid plaques, is derived by proteolytic cleavage from the amyloid precursor protein (APP). Epidemiologic and biochemical data suggest a link between cholesterol, APP processing, Ap, and Alzheimer's disease. Two recent epidemiologic studies indicate that there is a decreased prevalence of AD associated with the use of cholesterol-lowering drugs that inhibit 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoA reductase inhibitors or statins). Experiments in cell culture and in vivo demonstrate that treatment with statins reduces production of A beta. The authors discuss how cholesterol might modulate A beta deposit formation. As neurons receive only small amounts of exogenous cholesterol, statins that efficiently cross the blood-brain barrier may reduce the amount of neuronal cholesterol below a critical level. Decreased neuronal cholesterol levels inhibit the A beta -forming amyloidogenic pathway possibly by removing APP from cholesterol- and sphingolipid-enriched membrane microdomains. In addition, depletion of cellular cholesterol levels reduces the ability of A beta to act as a seed for further fibril formation. These intriguing relationships raise the hopes that cholesterol-lowering strategies may influence the progression of AD.