Cholesterol homeostasis in human brain: evidence for an age-dependent flux of 24S-hydroxycholesterol from the brain into the circulation

Proc Natl Acad Sci U S A. 1996 Sep 3;93(18):9799-804. doi: 10.1073/pnas.93.18.9799.


We have investigated whether side chain-hydroxylated cholesterol species 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 consistent with a net flux of this steroid from the brain into the circulation, corresponding to elimination of approximately 4 mg cholesterol during a 24-h period in adults. Results of experiments with rats exposed to 18O2 were also consistent with a flux of 24-OH-Chol from the brain into the circulation. No other oxysterol measured showed a similar behavior as 24-OH-Chol. These results and the finding that the concentration 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 24-OH-Chol present in the circulation originates from the brain. Both the 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 approximately 5 times higher during the first decade of life than during the sixth decade. There was a high correlation between levels of 24-OH-Chol in plasma and cerebrospinal fluid. It is suggested that the flux of 24-OH-Chol from the brain is important for cholesterol homeostasis in this organ.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aging / metabolism*
  • Animals
  • Brain / metabolism*
  • Child
  • Child, Preschool
  • Circadian Rhythm
  • Female
  • Homeostasis*
  • Humans
  • Hydroxycholesterols / blood
  • Hydroxycholesterols / cerebrospinal fluid
  • Hydroxycholesterols / metabolism*
  • Infant
  • Male
  • Middle Aged
  • Oxygen
  • Rats
  • Reference Values
  • Stereoisomerism
  • Tissue Distribution


  • Hydroxycholesterols
  • 24-hydroxycholesterol
  • Oxygen