Effects of simvastatin on cholesterol metabolism and Alzheimer disease biomarkers

Alberto Serrano-Pozo, Gloria L. Vega, Dieter Lütjohann, Joseph J. Locascio, Marsha K. Tennis, Amy Deng, Alireza Atri, Bradley T. Hyman, Michael C. Irizarry, John H. Growdon

Research output: Contribution to journalArticlepeer-review

54 Scopus citations


Preclinical and epidemiologic studies suggest a protective effect of statins on Alzheimer disease (AD). Experimental evidence indicates that some statins can cross the blood-brain barrier, alter brain cholesterol metabolism, and may ultimately decrease the production of amyloid-β (Aβ) peptide. Despite these promising leads, clinical trials have yielded inconsistent results regarding the benefits of statin treatment in AD. Seeking to detect a biological signal of statins effect on AD, we conducted a 12-week open-label trial with simvastatin 40? mg/d and then 80? mg/d in 12 patients with AD or amnestic mild cognitive impairment and hypercholesterolemia. We quantified cholesterol precursors and metabolites and AD biomarkers of Aβ and tau in both plasma and cerebrospinal fluid at baseline and after the 12-week treatment period. We found a modest but significant inhibition of brain cholesterol biosynthesis after simvastatin treatment, as indexed by a decrease of cerebrospinal fluid lathosterol and plasma 24S-hydroxycholesterol. Despite this effect, there were no changes in AD biomarkers. Our findings indicate that simvastatin treatment can affect brain cholesterol metabolism within 12 weeks, but did not alter molecular indices of AD pathology during this short-term treatment.

Original languageEnglish (US)
Pages (from-to)220-226
Number of pages7
JournalAlzheimer disease and associated disorders
Issue number3
StatePublished - 2010


  • Alzheimer disease
  • biomarker
  • cholesterol
  • simvastatin

ASJC Scopus subject areas

  • Clinical Psychology
  • Gerontology
  • Geriatrics and Gerontology
  • Psychiatry and Mental health


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