title: Effect of statins on Alzheimer's disease biomarkers in cerebrospinal fluid.
abstract: BACKGROUND
  Treatment with HMG-CoA reductase inhibitors ("statins") has been variably associated with a reduced risk of Alzheimer's disease (AD) in epidemiologic studies and reduced amyloid-beta (Abeta) deposition in animal models of AD. Putative neuroprotective effects of statins may vary in relation to their ability to penetrate into the central nervous system (CNS).
  
  
  METHODS
  We measured levels of cerebrospinal fluid (CSF) AD biomarkers following 14 weeks of treatment with simvastatin (a CNS permeant statin; n=10) at 40 mg/day or pravastatin (a CNS impermeant statin; n=13) at 80 mg/day in hypercholesterolemic subjects without dementia.
  
  
  RESULTS
  Simvastatin, but not pravastatin, reduced CSF levels of phospho-tau-181 (p-tau181) in all subjects. There were no differences in CSF levels of total tau, Abeta42, Abeta40, soluble amyloid beta protein precursor (sAbetaPP) alpha or beta, or F2-isoprostanes.
  
  
  CONCLUSIONS
  Statins may modulate the phosphorylation of tau in humans and this effect may depend on the CNS availability of the statin. These results suggest another mechanism by which statins may act to reduce the risk of AD.
authors.affiliation: Department of Medicine, Division of Geriatric Medicine, University of Washington School of Medicine, and VA Puget Sound Health Care System, Seattle, WA 98108, USA.
authors.forename: Robert G
authors.initials: RG
authors.lastname: Riekse
authors.forename: Ge
authors.initials: G
authors.lastname: Li
authors.forename: Eric C
authors.initials: EC
authors.lastname: Petrie
authors.forename: James B
authors.initials: JB
authors.lastname: Leverenz
authors.forename: Darcy
authors.initials: D
authors.lastname: Vavrek
authors.forename: Simona
authors.initials: S
authors.lastname: Vuletic
authors.forename: John J
authors.initials: JJ
authors.lastname: Albers
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Montine
authors.forename: Virginia M-Y
authors.initials: VM
authors.lastname: Lee
authors.forename: Michael
authors.initials: M
authors.lastname: Lee
authors.forename: Peter
authors.initials: P
authors.lastname: Seubert
authors.forename: Douglas
authors.initials: D
authors.lastname: Galasko
authors.forename: Gerard D
authors.initials: GD
authors.lastname: Schellenberg
authors.forename: William R
authors.initials: WR
authors.lastname: Hazzard
authors.forename: Elaine R
authors.initials: ER
authors.lastname: Peskind
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid* / Q000188:drug therapy; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid; D016564:Amyloid beta-Protein Precursor / Q000134:cerebrospinal fluid; D001921:Brain / Q000378:metabolism; D002784:Cholesterol / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D028441:F2-Isoprostanes / Q000134:cerebrospinal fluid; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000493:pharmacokinetics / Q000627:therapeutic use*; D006937:Hypercholesterolemia / Q000134:cerebrospinal fluid / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D018696:Neuroprotective Agents / Q000493:pharmacokinetics / Q000627:therapeutic use*; D010446:Peptide Fragments / Q000134:cerebrospinal fluid; D017035:Pravastatin / Q000493:pharmacokinetics / Q000627:therapeutic use*; D019821:Simvastatin / Q000493:pharmacokinetics / Q000627:therapeutic use*; D014280:Triglycerides / Q000097:blood; D016875:tau Proteins / Q000134:cerebrospinal fluid
chemical_list: D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D008078:Cholesterol, LDL; D028441:F2-Isoprostanes; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D018696:Neuroprotective Agents; D010446:Peptide Fragments; D014280:Triglycerides; C500436:amyloid beta-peptide (5-40); C075222:amyloid beta-protein (1-42); D016875:tau Proteins; D002784:Cholesterol; D019821:Simvastatin; D017035:Pravastatin