title: Lipid peroxidation is an early event in the brain in amnestic mild cognitive impairment.
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 F(2)-isoprostane (F(2)-IsoP) and F(4)-neuroprostane (F(4)-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 F(2)-IsoP and F(4)-NP levels. Significant increases in F(2)-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 F(4)-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 between MCI and late AD was significantly increased F(4)-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.
authors.affiliation: Alzheimer's Disease Research Center, Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY 40536, USA. wmark0@email.uky.edu
authors.forename: William R
authors.initials: WR
authors.lastname: Markesbery
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Kryscio
authors.forename: Mark A
authors.initials: MA
authors.lastname: Lovell
authors.forename: Jason D
authors.initials: JD
authors.lastname: Morrow
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism*; D001344:Autopsy / Q000379:methods; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D003072:Cognition Disorders / Q000378:metabolism*; D004281:Docosahexaenoic Acids / Q000378:metabolism; D028441:F2-Isoprostanes / Q000378:metabolism; D005260:Female; D006801:Humans; D015227:Lipid Peroxidation / Q000502:physiology*; D008297:Male; D008609:Mental Status Schedule / Q000706:statistics & numerical data
chemical_list: D028441:F2-Isoprostanes; D004281:Docosahexaenoic Acids