Simvastatin therapy prevents brain trauma-induced increases in β-amyloid peptide levels

Authors

  • Eric E. Abrahamson PhD,

    1. Department of Neurology, Brain Trauma Research Center, University of Pittsburgh School of Medicine, Pittsburgh, PA
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  • Milos D. Ikonomovic MD,

    1. Department of Neurology, Brain Trauma Research Center, University of Pittsburgh School of Medicine, Pittsburgh, PA
    2. Department of Psychiatry, Brain Trauma Research Center, University of Pittsburgh School of Medicine, Pittsburgh, PA
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  • C. Edward Dixon PhD,

    1. Department of Neurosurgery, Brain Trauma Research Center, University of Pittsburgh School of Medicine, Pittsburgh, PA
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  • Steven T. DeKosky MD

    Corresponding author
    1. Department of Neurology, Brain Trauma Research Center, University of Pittsburgh School of Medicine, Pittsburgh, PA
    2. Department of Psychiatry, Brain Trauma Research Center, University of Pittsburgh School of Medicine, Pittsburgh, PA
    3. University of Virginia School of Medicine, Charlottesville, VA
    • Office of the Dean, University of Virginia School of Medicine, PO Box 800793, Charlottesville, VA 22908-0793
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  • Potential conflict of interest: Nothing to report.

Abstract

Elevations in β-amyloid peptide (Aβ) levels after traumatic brain injury (TBI) may confer risk for developing Alzheimer's disease in head trauma patients. We investigated the effects of simvastatin, a 3-hydroxy-3-methylglutaryl-CoA reductase inhibitor, on hippocampal Aβ burden in a clinically relevant head injury/intervention model using mice expressing human Aβ. Simvastatin therapy blunted TBI-induced increases in Aβ, reduced hippocampal tissue damage and microglial activation, and improved behavioral outcome. The ability of statins to reduce post-injury Aβ load and ameliorate pathological sequelae of brain injury makes them potentially effective in reducing the risk of developing Alzheimer's disease in TBI patients. Ann Neurol 2009;66:407–414

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