title: Brain oxidative stress in a triple-transgenic mouse model of Alzheimer disease.
abstract: Alzheimer disease (AD) is a neurodegenerative disease which is characterized by the presence of extracellular senile plaques mainly composed of amyloid-beta peptide (Abeta), intracellular neurofibrillary tangles, and selective synaptic and neuronal loss. AD brains revealed elevated levels of oxidative stress markers which have been implicated in Abeta-induced toxicity. In the present work we addressed the hypothesis that oxidative stress occurs early in the development of AD and evaluated the extension of the oxidative stress and the levels of antioxidants in an in vivo model of AD, the triple-transgenic mouse, which develops plaques, tangles, and cognitive impairments and thus mimics AD progression in humans. We have shown that in this model, levels of antioxidants, namely, reduced glutathione and vitamin E, are decreased and the extent of lipid peroxidation is increased. We have also observed increased activity of the antioxidant enzymes glutathione peroxidase and superoxide dismutase. These alterations are evident during the Abeta oligomerization period, before the appearance of Abeta plaques and neurofibrillary tangles, supporting the view that oxidative stress occurs early in the development of the disease.
authors.affiliation: Institute of Biochemistry, Faculty of Medicine, University of Coimbra, 3004-504 Coimbra, Portugal.
authors.forename: Rosa
authors.initials: R
authors.lastname: Resende
authors.forename: Paula Isabel
authors.initials: PI
authors.lastname: Moreira
authors.forename: Teresa
authors.initials: T
authors.lastname: Proença
authors.forename: Atul
authors.initials: A
authors.lastname: Deshpande
authors.forename: Jorge
authors.initials: J
authors.lastname: Busciglio
authors.forename: Cláudia
authors.initials: C
authors.lastname: Pereira
authors.forename: Catarina Resende
authors.initials: CR
authors.lastname: Oliveira
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D005978:Glutathione / Q000378:metabolism; D015227:Lipid Peroxidation; D051379:Mice; D008822:Mice, Transgenic; D018384:Oxidative Stress; D058225:Plaque, Amyloid / Q000378:metabolism / Q000473:pathology; D014810:Vitamin E / Q000378:metabolism
chemical_list: D000975:Antioxidants; D014810:Vitamin E; D005978:Glutathione