Can statins put the brakes on Alzheimer's disease?

摘要

Statins inhibit 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase,which initiates the syntheses of cholesterol and isoprenoid lipids that are needed to provide amyloid peptides for the amyloid cascade.This cascade is believed to induce sporadic or late-onset Alzheimer's disease,which accounts for 90-95% of Alzheimer's disease sufferers.Cholesterol is also the prime driver of cerebrovascular disease that (along with amyloid peptides) increasingly appears to be linked to the cognitive deterioration of Alzheimer's disease.Cholesterol is needed to make the lipid rafts that are the platforms for isoprenoid-dependent assembly and activation of raftophilic beta-and gamma-secre-tases that work in tandem to excise dangerous 40 and 42 amino acid amy-loid-beta (A beta) fragments from amyloid precursor protein,the transmembrane amyloid precursor glycoprotein.When they are excessively produced and can no longer be effectively destroyed or otherwise cleared from the hypo-perfused ageing brain,the A beta42 fragments released from the active synaptic terminals of normally busy neurons (and from stressed neurons unsuccessfully trying to proliferate and producing disruptive tangles of hyper-phosphorylated tau-proteins) aggregate into neuritic plaques,which activate glial cells.The pro-inflammatory cytokines and growth factors from the glial cells further damage and kill neurons.As statins strike at several parts of the Alzheimer's disease mechanism (such as the infliction of cholesterol-dependent cerebrovascular damage) by inhibiting HMG-CoA reductase,their long-term use (starting as early as possible during Alzheimer's disease development) should slow or even prevent the progression of Alzheimer's disease.Indeed,there is some evidence of a significantly reduced incidence of Alzheimer's disease among people who have been using statins to reduce hyper-cholesterolaemia and its cardiovascular effects.To be certain of this,there must be more multi-year trials to specifically assess the effects of statins on sporadic Alzheimer's disease.