title: Oxysterols and cholesterol precursors correlate to magnetic resonance imaging measures of neurodegeneration in multiple sclerosis.
abstract: BACKGROUND
  Cholesterol homeostasis is important for formation and maintenance of myelin and axonal membranes in the central nervous system (CNS). The concentrations of the brain specific cholesterol metabolite 24S-hydroxycholesterol (24OHC) and cholesterol precursors have been shown to be altered in multiple sclerosis (MS). However, how changes in sterol levels relate to the pathological processes in MS is not clear.
  
  
  METHODS
  In this study, we compared serum and cerebrospinal fluid (CSF) sterol levels between 105 MS (51 relapsing-remitting (RR); 39 secondary progressive (SP) and 15 primary progressive (PP)) and 49 control patients. Sterol levels were correlated to magnetic resonance imaging (MRI) markers of disease activity.
  
  
  RESULTS
  We found decreased serum 24OHC and 27-hydroxycholesterol (27OHC) and increased CSF lathosterol in MS patients compared to control patients (p=0.018, p=0.002 and p=0.002, respectively). Subgroup analysis showed that serum 24OHC levels were negatively correlated to normalized brain volume measurements in relapse-onset MS patients (r= -0.326, p=0.004).
  
  
  CONCLUSIONS
  These results confirm that cholesterol homeostasis is disturbed in MS and suggest that changes in cholesterol synthesis are related to neurodegenerative pathological processes as seen on the MRI. The data seem to be in line with the recently reported observation that high dose statins may have a positive effect on clinical disability in secondary progressive MS.
authors: Department of Neurology, MS Center Amsterdam, VU University Medical Center,  The Netherlands.
authors: C
authors: C
authors: van de Kraats
authors: J
authors: J
authors: Killestein
authors: V
authors: V
authors: Popescu
authors: E
authors: E
authors: Rijkers
authors: H
authors: H
authors: Vrenken
authors: D
authors: D
authors: Lütjohann
authors: F
authors: F
authors: Barkhof
authors: C H
authors: CH
authors: Polman
authors: C E
authors: CE
authors: Teunissen
mesh_terms: D000328:Adult; D001921:Brain / Q000473:pathology*; D002784:Cholesterol / Q000097:blood / Q000134:cerebrospinal fluid / Q000378:metabolism*; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D006706:Homeostasis / Q000502:physiology*; D006801:Humans; D006888:Hydroxycholesterols / Q000097:blood / Q000134:cerebrospinal fluid; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000378:metabolism* / Q000473:pathology*; D009410:Nerve Degeneration / Q000378:metabolism / Q000473:pathology
chemical_list: D006888:Hydroxycholesterols; C044563:24-hydroxycholesterol; C076996:27-hydroxycholesterol; C001521:lathosterol; D002784:Cholesterol
keywords: Multiple sclerosis; cholesterol; magnetic resonance imaging; statins