title: Amyloid Plaque-Associated Oxidative Degradation of Uniformly Radiolabeled Arachidonic Acid.
abstract: Oxidative stress is a frequently observed feature of Alzheimer's disease, but its pathological significance is not understood. To explore the relationship between oxidative stress and amyloid plaques, uniformly radiolabeled arachidonate was introduced into transgenic mouse models of Alzheimer's disease via intracerebroventricular injection. Uniform labeling with carbon-14 is used here for the first time, and made possible meaningful quantification of arachidonate oxidative degradation products. The injected arachidonate entered a fatty acid pool that was subject to oxidative degradation in both transgenic and wild-type animals. However, the extent of its degradation was markedly greater in the hippocampus of transgenic animals where amyloid plaques were abundant. In human Alzheimer's brain, plaque-associated proteins were post-translationally modified by hydroxynonenal, a well-known oxidative degradation product of arachidonate. These results suggest that several recurring themes in Alzheimer's pathogenesis, amyloid β proteins, transition metal ions, oxidative stress, and apolipoprotein isoforms, may be involved in a common mechanism that has the potential to explain both neuronal loss and fibril formation in this disease.
authors.affiliation: Department of Pharmacology, The University of Pennsylvania , Philadelphia, Pennsylvania 19104, United States.
authors.forename: Ran
authors.initials: R
authors.lastname: Furman
authors.affiliation: Department of Neuroscience and Experimental Therapeutics, Texas A & M University , College Station, Texas 77807, United States.|Department of Physiology and Neuroscience, St. George's University , St. George's, Grenada.
authors.forename: Ian V J
authors.initials: IV
authors.lastname: Murray
authors.affiliation: Department of Neuroscience and Experimental Therapeutics, Texas A & M University , College Station, Texas 77807, United States.
authors.forename: Hayley E
authors.initials: HE
authors.lastname: Schall
authors.affiliation: Department of Pharmacology, The University of Pennsylvania , Philadelphia, Pennsylvania 19104, United States.
authors.forename: Qiwei
authors.initials: Q
authors.lastname: Liu
authors.affiliation: Department of Neuroscience and Experimental Therapeutics, Texas A & M University , College Station, Texas 77807, United States.
authors.forename: Yonatan
authors.initials: Y
authors.lastname: Ghiwot
authors.affiliation: Department of Pharmacology, The University of Pennsylvania , Philadelphia, Pennsylvania 19104, United States.
authors.forename: Paul H
authors.initials: PH
authors.lastname: Axelsen
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D004195:Disease Models, Animal; D005455:Fluorescent Antibody Technique; D006624:Hippocampus / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D013058:Mass Spectrometry; D051379:Mice; D008822:Mice, Transgenic; D018384:Oxidative Stress / Q000502:physiology; D058225:Plaque, Amyloid / Q000378:metabolism*
chemical_list: D016229:Amyloid beta-Peptides; D016718:Arachidonic Acid
keywords: Alzheimer’s disease; Oxidative stress; polyunsaturated fatty acids