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Publication : Increased plaque burden in brains of APP mutant MnSOD heterozygous knockout mice.

First Author  Li F Year  2004
Journal  J Neurochem Volume  89
Issue  5 Pages  1308-12
PubMed ID  15147524 Mgi Jnum  J:92214
Mgi Id  MGI:3051958 Doi  10.1111/j.1471-4159.2004.02455.x
Citation  Li F, et al. (2004) Increased plaque burden in brains of APP mutant MnSOD heterozygous knockout mice. J Neurochem 89(5):1308-12
abstractText  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.
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