Neurodegenerative disorders and cholesterol.

It has been suggested that a high serum cholesterol level is a risk factor for Alzheimer's disease (AD), that treatment with cholesterol-lowering drugs (statins) reduces the frequency of AD development, and that the polymorpholism of genes encoding proteins regulating cholesterol metabolism is associated with the frequency of AD development. However, the mechanism by which high serum cholesterol level leads to AD, still remains unclarified. Several recent studies have shown the results challenging the above notions. Here another notion is proposed, that is, a low high-density lipoprotein (HDL) level in serum and cerebro-spinal fluid (CSF) is a risk factor for the development of AD; moreover, the possibility that AD and Niemann-Pick type C disease share a common cascade, by which altered cholesterol metabolism leads to neurodegeneration (tauopathy) is discussed. In this review, the association between cholesterol and AD pathogenesis is discussed from different viewpoints and several basic issues are delineated and addressed to fully understand the mechanisms underlying this relationship.