Diagnostic use of cerebral and extracerebral oxysterols.
BACKGROUND
24S-Hydroxycholesterol (24OHC) and 27-hydroxycholesterol (27OHC) are two structurally similar oxysterols of different origins--the former almost exclusively formed in the brain and the latter formed to a lesser extent in the brain than in most other organs. HYPOTHESIS TO BE TESTED: Neuronal damage and/or demyelination causes increased flux of 24OHC from the brain into the cerebrospinal fluid (CSF), whereas a defect blood-brain barrier causes increased flux of 27OHC from the circulation into the CSF.


METHODS
Isotope dilution-mass spectrometry was used to assay the two oxysterols in CSF and plasma from more than 250 patients with different neurological and geriatric diseases.


RESULTS
The CSF-levels of the two oxysterols were much more affected by the different diseases than the plasma levels. Patients with active demyelinating diseases had increased levels of 24OHC in CSF with a relatively high 24OHC/27OHC ratio. Patients with meningitis in general had high levels of both steroids with a low 24OHC/27OHC ratio. Patients with Alzheimer's disease had slightly increased levels of 24OHC in CSF with less increase in 27OHC. Patients with multiple sclerosis had a tendency to have higher levels of 24OHC during active periods with a high 24OHC/ 27OHC ratio.


CONCLUSIONS
Measurements of the two oxysterols in CSF and plasma may add significantly to existing biochemical methods for evaluation of neurological diseases.
Leoni
Valerio
V
Department of Experimental and Clinical Biomedical Science (DSBSC), University of Insubria, Varese, Italy.
Masterman
Thomas
T
Mousavi
Fariba S
FS
Wretlind
Bengt
B
Wahlund
Lars-Olof
LO
Diczfalusy
Ulf
U
Hillert
Jan
J
Björkhem
Ingemar
I
D000328:Adult; D000368:Aged; D001927:Brain Diseases / Q000097:blood / Q000134:cerebrospinal fluid* / Q000175:diagnosis*; D005260:Female; D006801:Humans; D006888:Hydroxycholesterols / Q000097:blood / Q000134:cerebrospinal fluid*; D008297:Male; D008875:Middle Aged
D006888:Hydroxycholesterols; C044563:24-hydroxycholesterol; C076996:27-hydroxycholesterol