CHOLESTEROL HOMEOSTASIS IN HUMAN BRAIN - EVIDENCE FOR AN AGE-DEPENDENT FLUX OF 24S-HYDROXYCHOLESTEROL FROM THE BRAIN INTO THE CIRCULATION

We have investigated whether side chain-hydroxylated cholesterol speci es are important for elimination of cholesterol from the brain. Plasma concentrations of 24-hydroxycholesterol (24-OH-Chol) in the internal jugular vein and the brachial artery in healthy volunteers were consis tent with a net flux of this steroid from the brain into the circulati on, corresponding to elimination of approximate to 4 mg cholesterol du ring a 24-h period in adults. Results of experiments with rats exposed to O-18(2) were also consistent with a flux of 24-OH-Chol from the br ain into the circulation. No other oxysterol measured showed a similar behavior as 24-OH-Chol. These results and the finding that the concen tration of 24-OH-Chol was 30- to 1500-fold higher in the brain than in any other organ except the adrenals indicate that the major part of 2 4-OH-Chol present in the circulation originates from the brain. Both t he 24-OH-Chol present in the brain and in the circulation were the 24S -stereoisomer. In contrast to other oxysterols, levels of plasma 24-OH -Chol were found to be markedly dependent upon age. The ratio between 24-OH-Chol and cholesterol in plasma was approximate to 5 times higher during the first decade of life than during the sixth decade. There w as a high correlation between levels of 24-OH-Chol in plasma and cereb rospinal fluid. It is suggested that the flux of 24-OH-Chol from the b rain is important for cholesterol homeostasis in this organ.