title: Long-term statin therapy and CSF cholesterol levels: implications for Alzheimer's disease.
abstract: OBJECTIVE
  It is not yet established whether statins (lipophilic or hydrophilic) reduce the risk of Alzheimer's disease and, if so, by differentially modifying brain lipid levels. Our aim was to assess changes in brain cholesterol metabolism as reflected in the cerebrospinal fluid (CSF) before and after treatment with either atorvastatin or simvastatin.
  
  
  METHODS
  We carried out a longitudinal analysis of CSF cholesterol, lathosterol and 24(S)-hydroxycholesterol before and after treatment with maximum doses of statins in 10 asymptomatic subjects, 8 of whom were heterozygous for apolipoprotein E epsilon4, and in 6 presymptomatic PS1 subjects.
  
  
  RESULTS
  Statins initially reduced CSF lathosterol cholesterol and 24(S)-hydroxycholesterol in both PS1 and non-PS1 subjects reaching a nadir at 6-7 months, followed by a return to baseline at 15 months with an overshoot at 2 years, tending to return to baseline thereafter.
  
  
  CONCLUSIONS
  Possible long-term protective effects of statins are not likely largely related to the temporally-dependent biphasic effects of statin therapy upon the magnitude and direction of changes in CSF lipid levels and their subsequent return to baseline levels.
authors.affiliation: Proteomics and Mass Spectrometry Facility, University of Massachusetts Medical School, Worcester, Massachusetts 01655, USA.
authors.forename: Barbara A
authors.initials: BA
authors.lastname: Evans
authors.forename: James E
authors.initials: JE
authors.lastname: Evans
authors.forename: Stephen P
authors.initials: SP
authors.lastname: Baker
authors.forename: Kevin
authors.initials: K
authors.lastname: Kane
authors.forename: Joan
authors.initials: J
authors.lastname: Swearer
authors.forename: Douglas
authors.initials: D
authors.lastname: Hinerfeld
authors.forename: Richard
authors.initials: R
authors.lastname: Caselli
authors.forename: Ekaterina
authors.initials: E
authors.lastname: Rogaeva
authors.forename: Peter
authors.initials: P
authors.lastname: St George-Hyslop
authors.forename: Majaz
authors.initials: M
authors.lastname: Moonis
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Pollen
mesh_terms: D000328:Adult; D000368:Aged; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid* / Q000517:prevention & control*; D001057:Apolipoproteins E / Q000235:genetics; D000069059:Atorvastatin; D002784:Cholesterol / Q000134:cerebrospinal fluid*; D005260:Female; D006538:Heptanoic Acids / Q000627:therapeutic use; D006579:Heterozygote; D006801:Humans; D006888:Hydroxycholesterols / Q000134:cerebrospinal fluid; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D010865:Pilot Projects; D053764:Presenilin-1 / Q000235:genetics; D011758:Pyrroles / Q000627:therapeutic use; D019821:Simvastatin / Q000627:therapeutic use
chemical_list: D001057:Apolipoproteins E; D006538:Heptanoic Acids; D006888:Hydroxycholesterols; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D053764:Presenilin-1; D011758:Pyrroles; C001521:lathosterol; D002784:Cholesterol; D000069059:Atorvastatin; D019821:Simvastatin