Cholesterol, statins and tau

Many of the known risk factors for Alzheimer's disease (AD) are associated with cholesterol metabolism. Interestingly, it seems as if higher doses of statins, i.e. inhibitors of the cholesterol biosynthesis by blocking formation of mevalonate, might lower the progression of AD. The mechanisms, however, by which statins or cholesterol levels exert their influence are unknown. A hereditary cholesterol-storage disorder, Niemann Pick C, shows Alzheimer-like taupathology in youth or adolescence but with no amyloid plaques. This gives rise to the possibility that disturbances in cholesterol metabolism induce changes in tau without interposition of A beta-protein aggregates. Experimental data suggest that manipulation of cholesterol levels may lead to changes in tau phosphorylation. These changes vary depending on how cholesterol metabolism is manipulated. Effects seem to be either mild and transient, or drastic and related to neurodegeneration, or independent of the mevalonate pathway.