Lipid peroxidation is an early event in the brain in amnestic mild cognitive impairment

Authors

  • William R. Markesbery MD,

    Corresponding author
    1. Alzheimer's Disease Research Center, Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY
    2. Department of Pathology, University of Kentucky, Lexington, KY
    3. Department of Neurology, University of Kentucky, Lexington, KY
    • Sanders-Brown Center on Aging, University of Kentucky College of Medicine, 800 South Limestone, Lexington, KY 40536
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  • Richard J. Kryscio PhD,

    1. Alzheimer's Disease Research Center, Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY
    2. Department of Statistics, University of Kentucky, Lexington, KY
    3. Department of Public Health, University of Kentucky, Lexington, KY
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  • Mark A. Lovell PhD,

    1. Alzheimer's Disease Research Center, Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY
    2. Department of Chemistry, University of Kentucky, Lexington, KY
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  • Jason D. Morrow MD

    1. Division of Clinical Pharmacology, Departments of Pharmacology and Medicine, Vanderbilt University School of Medicine, Nashville, TN
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Abstract

Multiple studies demonstrate that the brain in Alzheimer's disease (AD) contains extensive oxidative damage. Most of these studies used advanced-stage AD patients raising the question of whether oxidative damage is a late effect of neurodegeneration or precedes and contributes to the pathogenesis of AD. Here we describe F2-isoprostane (F2-IsoP) and F4-neuroprostane (F4-NP) levels in longitudinally followed, well documented autopsied normal control subjects and patients with amnestic mild cognitive impairment (MCI), and late-stage AD. Gas chromatography/negative ion chemical ionization/mass spectrometry was used to determine F2-IsoP and F4-NP levels. Significant increases in F2-IsoP levels were found in frontal, parietal and occipital lobes in MCI and late AD compared to controls but no significant differences were present between MCI and late AD. A significant increase in F4-NPs was present in parietal and occipital lobes in MCI compared to controls and a significant increase was present in these regions and hippocampus in late AD compared to controls. The only difference betwen MCI and late AD was significantly increased F4-NP in hippocampus in late AD. Our data indicate that lipid peroxidation is present in the brain of MCI patients and suggest that oxidative damage may play a role in the pathogenesis of AD. Ann Neurol 2005;58:730–735

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