Relationship between the plasma low-density lipoprotein cholesterol concentration and sterol metabolism in the central nervous system

It has been postulated that the function of the brain may depend on the concentration of cholesterol in the plasma carried in low-density lipoproteins. However, all animals synthesize the cholesterol that they require for the daily turnover of cell membrane sterol. In most species, and particularly in the primate, the great majority of this synthetic activity is located in the extrahepatic organs. During development of the fetus and newborn animal, this cholesterol is used for organ growth. In the brain, however, there is both growth of the organ and increasing concentrations of tissue sterol. Rates of cholesterol synthesis are very high in the brain of the developing fetus and newborn animal, but these rates drop to essentially zero once the brain attains its mature size. The uptake of plasma low-density lipoprotein cholesterol into the brain is essentially zero, and there is no difference in the concentration of cholesterol in the brain of animals lacking low-density lipoprotein receptor activity. These findings are consistent with the view that virtually all cholesterol in the central nervous system is synthesized locally and that metabolism of sterol within the brain is independent of changes in the circulating plasma cholesterol level.