title: 7α-hydroxy-3-oxo-4-cholestenoic acid in cerebrospinal fluid reflects the integrity of the blood-brain barrier.
abstract: There is a continuous flux 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 7α-hydroxy-3-oxo-4-cholestenoic acid (7-HOCA). We confirm a recent report describing the presence of this metabolite in cerebrospinal fluid (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)H4-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.
authors: Division of Clinical Chemistry, Department of Laboratory Medicine, Karolinska Institute, Stockholm, Sweden.
authors: Ahmed
authors: A
authors: Saeed
authors: Federico
authors: F
authors: Floris
authors: Ulla
authors: U
authors: Andersson
authors: Irina
authors: I
authors: Pikuleva
authors: Anita
authors: A
authors: Lövgren-Sandblom
authors: Maria
authors: M
authors: Bjerke
authors: Martin
authors: M
authors: Paucar
authors: Anders
authors: A
authors: Wallin
authors: Per
authors: P
authors: Svenningsson
authors: Ingemar
authors: I
authors: Björkhem
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000134:cerebrospinal fluid; D001812:Blood-Brain Barrier / Q000473:pathology* / Q000503:physiopathology*; D002783:Cholestenones / Q000134:cerebrospinal fluid*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged
chemical_list: D015415:Biomarkers; D002783:Cholestenones; C056891:7 alpha-hydroxy-3-oxo-4-cholestenoic acid
keywords: 27-hydroxycholesterol; CYP7B1; brain cholesterol homeostasis