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2990211 
Journal Article 
Increased plaque burden in brains of APP mutant MnSOD heterozygous knockout mice 
Li, F; Calingasan, NY; Yu, F; Mauck, WM; Toidze, M; Almeida, CG; Takahashi, RH; Carlson, GA; Flint Beal, M; Lin, MT; Gouras, GK 
2004 
Yes 
Journal of Neurochemistry
ISSN: 0022-3042
EISSN: 1471-4159 
WILEY 
HOBOKEN 
89 
5 
1308-1312 
English 
15147524 
WOS:000221437200025 
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.