Long-Term Statin Therapy and CSF Cholesterol Levels: Implications for Alzheimer’s DiseaseEvans B.A.a · Evans J.E.a · Baker S.P.c · Kane K.b · Swearer J.b · Hinerfeld D.d · Caselli R.e · Rogaeva E.f · St. George-Hyslop P.f · Moonis M.b · Pollen D.A.b
aProteomics and Mass Spectrometry Facility, and bDepartment of Neurology, University of Massachusetts Medical School, and cBioinformatics Unit, Information Service and Department of Cell Biology, Worcester, Mass., dJackson Laboratory, Bar Harbor, Me., and eDepartment of Neurology, Mayo Clinic, Scottsdale, Ariz., USA; fDivision of Neurology, Department of Medicine, University of Toronto and Toronto Western Hospital, Toronto, Ont., Canada
Background/Aims: 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 ε4, 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.
Copyright © 2009 S. Karger AG, Basel
Dr. Dan Pollen
Department of Neurology, University of Massachusetts Medical School
55 Lake Ave.
N. Worcester, MA 01655 (USA)
D.P., the corresponding author, had full access to all the data in the study and had final responsibility for the decision to submit for publication.
Accepted: March 7, 2009
Published online: May 29, 2009
Number of Print Pages : 6
Number of Figures : 1, Number of Tables : 2, Number of References : 28
Dementia and Geriatric Cognitive Disorders
Vol. 27, No. 6, Year 2009 (Cover Date: July 2009)
Journal Editor: Chan-Palay V. (New York, N.Y.)
ISSN: 1420-8008 (Print), eISSN: 1421-9824 (Online)
For additional information: http://www.karger.com/DEM