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(American Journal of Pathology. 1999;155:863-868.)
© 1999 American Society for Investigative Pathology

Regular Articles

The Magnitude of Brain Lipid Peroxidation Correlates with the Extent of Degeneration but Not with Density of Neuritic Plaques or Neurofibrillary Tangles or with APOE Genotype in Alzheimer's Disease Patients

Thomas J. Montine^||, William R. Markesbery^§, William Zackert, Stephanie C. Sanchez, L. Jackson Roberts, II^* and Jason D. Morrow^*

From the Departments of Medicine,^*
Pathology,^||
and Pharmacology
and the Center for Molecular Neurosciences,
Vanderbilt University Medical Center, Nashville, Tennessee; and the Sanders-Brown Center on Aging^§
and the Departments of Pathology and Neurology, University of Kentucky Medical Center, Lexington, Kentucky

Numerous post mortem studies have demonstrated increased accumulation of lipid peroxidation products in diseased regions of Alzheimer's disease (AD) brain; however, few have used techniques that quantify the magnitude of lipid peroxidation in vivo. F₂-isoprostanes (F₂-IsoP's) are exclusive products of free radical-mediated peroxidation of arachidonic acid, and their quantification has been widely used as an in vivo biomarker of the magnitude of lipid peroxidation. We have determined F₂-IsoP concentrations in lateral ventricular fluid (VF) from 23 AD and 12 age-matched controls and correlated these with neuropathological and genetic markers of AD. VF F₂-IsoP levels were significantly elevated in AD patients compared with controls (p < 0.01) and were significantly correlated with three different measures of brain degeneration: reduction in brain weight (p < 0.01), degree of cortical atrophy (p < 0.01), and Braak stage (p = 0.02). When analysis was restricted to AD patients only, VF F₂-IsoP levels still were significantly correlated to reduction in brain weight and degree of cortical atrophy (p < 0.05). VF F₂-IsoP concentrations were not related to density of neuritic plaques or neurofibrillary tangles in seven brain regions, or to the number of 4 alleles of the apolipoprotein E gene (APOE). These data suggest that the magnitude of brain lipid peroxidation is closely related to the extent of brain degeneration in AD but is not significantly influenced by the density of neuritic plaques or neurofibrillary tangles, or the number of 4 alleles of APOE.

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