Effect of statins on Alzheimer's disease biomarkers in cerebrospinal fluid

Robert G. Riekse, Ge Li, Eric C. Petrie, James B. Leverenz, Darcy Vavrek, Simona Vuletic, John J. Albers, Thomas J. Montine, Virginia M.Y. Lee, Michael Lee, Peter Seubert, Douglas Galasko, Gerard D. Schellenberg, William R. Hazzard, Elaine R. Peskind

Research output: Contribution to journalArticlepeer-review

90 Scopus citations


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-β (Aβ) 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, Aβ42, Aβ40, soluble amyloid β protein precursor (sAβPP) α or β, 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.

Original languageEnglish (US)
Pages (from-to)399-406
Number of pages8
JournalJournal of Alzheimer's Disease
Issue number4
StatePublished - 2006


  • Alzheimer's disease
  • CSF
  • Clinical trial
  • Statins
  • Tau


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