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(American Journal of Pathology. 2001;158:293-297.)
© 2001 American Society for Investigative Pathology

Regular Articles

Brain Regional Quantification of F-Ring and D-/E-Ring Isoprostanes and Neuroprostanes in Alzheimer’s Disease

Erin E. Reich^*, William R. Markesbery^¶, L. Jackson Roberts, II^*, Larry L. Swift, Jason D. Morrow^* and Thomas J. Montine^*§

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

Isoprostanes (IsoP) are produced exclusively from free radical damage to arachidonic acid, a fatty acid that is evenly distributed throughout white matter and gray matter, whereas neuroprostanes (NPs) are generated analogously from docosahexaenoic acid (DHA), a fatty acid enriched in gray matter where it is concentrated in neurons. IsoP and NPs derive from endoperoxide intermediates that isomerize to D/E-ring forms or that are reduced to F-ring compounds. We quantified F-ring and D/E-ring IsoP and NPs in temporal and parietal cortex, hippocampus, and cerebellum of nine definite Alzheimer’s disease (AD) patients and 11 age-matched controls. Total NP levels (F-ring plus D/E-ring), but not total IsoP, were significantly greater in AD than controls (P < 0.0001); only cerebral regions in AD patients had NPs greater than controls (P < 0.05). The F-ring to D/E-ring ratio for NPs, but not IsoP, was 40 to 70% lower in all brain regions of AD patients compared to controls (P < 0.005). These data extend results from in situ techniques, that have localized reactive products of lipid peroxidation primarily to neurons, by quantifying significantly greater free radical damage to the DHA-containing compartments in cerebrum in AD patients than controls, and suggest that one mechanism of increased oxidative stress may be diminished reducing capacity in DHA-containing compartments.

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