Brain regional quantification of F-ring and D-/E-ring isoprostanes and neuroprostanes in Alzheimer's disease

Isoprostanes (IsoP) are produced exclusively from free radical damage to ar achidonic acid, a fatty acid that is evenly distributed throughout white ma tter and gray matter, whereas neuroprostanes (NPs) are generated analogousl y from docosahexaenoic acid (DHA), a fatty acid enriched in gray matter whe re it is concentrated in neurons. IsoP and NPs derive from endoperoxide int ermediates that isomerize to D/E-ring forms or that are reduced to F-ring c ompounds. We quantified F-ring and D/E-ring IsoP and NPs in temporal and pa rietal cortex, hippocampus, and cerebellum of nine definite Alzheimer's dis ease (AD) patients and 11 age-matched controls. Total NP levels (F-ring plu s D/E-ring), but not total IsoP, were significantly greater in AD than cont rols (P < 0.0001); only cerebral regions in AD patients had NPs greater tha n 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 control s (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-containin g compartments in cerebrum in AD patients than controls, and suggest that o ne mechanism of increased oxidative stress may be diminished reducing capac ity in DHA-containing compartments.