title: Increased plaque burden in brains of APP mutant MnSOD heterozygous knockout mice.
abstract: A growing body of evidence suggests a relationship between oxidative stress and beta-amyloid (Abeta) peptide accumulation, a hallmark in the pathogenesis of Alzheimer's disease (AD). However, a direct causal relationship between oxidative stress and Abeta pathology has not been established in vivo. Therefore, we crossed mice with a knockout of one allele of manganese superoxide dismutase (MnSOD), a critical antioxidant enzyme, with Tg19959 mice, which overexpress a doubly mutated human beta-amyloid precursor protein (APP). Partial deficiency of MnSOD, which is well established to cause elevated oxidative stress, significantly increased brain Abeta levels and Abeta plaque burden in Tg19959 mice. These results indicate that oxidative stress can promote the pathogenesis of AD and further support the feasibility of antioxidant approaches for AD therapy.
authors.affiliation: Department of Neurology and Neuroscience, Weill Medical College of Cornell University, 525 East 68th Street, New York, NY 10021, USA.
authors.forename: Feng
authors.initials: F
authors.lastname: Li
authors.forename: Noel Y
authors.initials: NY
authors.lastname: Calingasan
authors.forename: Fangmin
authors.initials: F
authors.lastname: Yu
authors.forename: William M
authors.initials: WM
authors.lastname: Mauck
authors.forename: Marine
authors.initials: M
authors.lastname: Toidze
authors.forename: Claudia G
authors.initials: CG
authors.lastname: Almeida
authors.forename: Reisuke H
authors.initials: RH
authors.lastname: Takahashi
authors.forename: George A
authors.initials: GA
authors.lastname: Carlson
authors.forename: M
authors.initials: M
authors.lastname: Flint Beal
authors.forename: Michael T
authors.initials: MT
authors.lastname: Lin
authors.forename: Gunnar K
authors.initials: GK
authors.lastname: Gouras
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000096:biosynthesis / Q000235:genetics*; D000818:Animals; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D003433:Crosses, Genetic; D004195:Disease Models, Animal; D018450:Disease Progression; D006579:Heterozygote; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008817:Mice, Mutant Strains; D018384:Oxidative Stress / Q000235:genetics; D058225:Plaque, Amyloid / Q000235:genetics* / Q000473:pathology; D013482:Superoxide Dismutase / Q000172:deficiency* / Q000235:genetics
chemical_list: D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D013482:Superoxide Dismutase