Cholesterol metabolism in the brain

The central nervous system accounts for only 2% of the whole body mass but contains almost a quarter of the unesterified cholesterol present in the wh ole individual. This sterol is largely present in two pools comprised of th e cholesterol in the plasma membranes of glial cells and neurons and the ch olesterol present in the specialized membranes of myelin. From 0.02% (human ) to 0.4% (mouse) of the cholesterol in these pools turns over each day so that the absolute flux of sterol across the brain is only approximately 0.9 % as rapid as the turnover of cholesterol in the whole body of these respec tive species. The input of cholesterol into the central nervous system come s almost entirely from in situ synthesis, and there is currently little evi dence for the net transfer of sterol from the plasma into the brain of the fetus, newborn or adult. In the steady state in the adult, an equivalent am ount of cholesterol must move out of the brain and this output is partly ac counted for by the formation and excretion of 24S-hydroxycholesterol. This cholesterol turnover across the brain is increased in neurodegenerative dis orders such as Alzheimer's disease and Niemann-Pick type C disease, Indirec t evidence suggests that large amounts of cholesterol also turn over among the glial cells and neurons within the central nervous system during brain growth and neuron repair and remodelling. This internal recycling of sterol may involve ligands such as apolipoproteins E and Al, and one or more memb rane transport proteins such as members of the low density lipoprotein rece ptor family. Changes in cholesterol balance across the whole body may, in s ome way, cause alterations in sterol recycling and apolipoprotein E express ion within the central nervous system, which, in turn; may affect neuron an d myelin integrity. Further elucidation of the processes controlling these events is very important to understand a variety of neurodegenerative disor ders. Curr Opin Lipidol 12:105-112. (C) 2001 Lippincott Williams & Wilkins.