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 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.
Reich
E E
EE
Department of Pharmacology, Vanderbilt University Medical Center, Nashville, Tennessee 37232, USA.
Markesbery
W R
WR
Roberts
L J
LJ
Swift
L L
LL
Morrow
J D
JD
Montine
T J
TJ
D000483:Alleles; D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism*; D000704:Analysis of Variance; D053327:Apolipoprotein E4; D001057:Apolipoproteins E / Q000235:genetics; D016718:Arachidonic Acid / Q000378:metabolism; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D001923:Brain Chemistry; D015237:Dinoprost / Q000737:chemistry / Q000378:metabolism*; D015232:Dinoprostone / Q000378:metabolism*; D004281:Docosahexaenoic Acids / Q000378:metabolism; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male
D053327:Apolipoprotein E4; D001057:Apolipoproteins E; D004281:Docosahexaenoic Acids; D016718:Arachidonic Acid; D015237:Dinoprost; D015232:Dinoprostone