7 α-hydroxy-3-oxo-4-cholestenoic acid in cerebrospinal fl uid refl ects the integrity of the blood-brain barrier

Abstract

Abstract There is a continuous fl ux of the oxysterol 27- hydroxycholesterol (27-OHC) from the circulation across the blood-brain barrier (BBB) into the brain. The major metabolite of 27-OHC in the brain is 7 α -hydroxy-3-oxo-4- cholestenoic acid (7-HOCA). We confirm a recent report describing the presence of this metabolite in cerebrospinal fl uid (CSF) at a relatively high concentration. A simple and accurate method was developed for assay of 7-HOCA in CSF based on isotope dilution-mass spectrometry and use of 2 H 4 -labeled internal standard. The concentration of this metabolite was found to be markedly increased in CSF from patients with a dysfunctional BBB. There was a high correlation between the levels of 7-HOCA in CSF and the CSF/serum albumin ratio. The concentration of 7-HOCA in CSF was not significantly affected by neurodegeneration. Our findings suggest that 7-HOCA could be used as a diagnostic marker for conditions with a dysfunctional BBB. -Saeed, A., F. Floris, U. Andersson, I. Pikuleva, A. LÖvgren-Sandblom, M. Bjerke, M. Paucar, A. Wallin, P. Svenningsson, and I. BjÖrkhem. 7 α -hydroxy-3-oxo-4-cholestenoic acid in cerebrospinal fl uid refl ects the integrity of the blood-brain barrier. Copyright © 2014 by the American Society for Biochemistry and Molecular Biology, Inc..