Increased plaque burden in brains of APP mutant MnSOD heterozygous knockout mice
Open Access
- 26 April 2004
- journal article
- Published by Wiley in Journal of Neurochemistry
- Vol. 89 (5), 1308-1312
- https://doi.org/10.1111/j.1471-4159.2004.02455.x
Abstract
A growing body of evidence suggests a relationship between oxidative stress and β-amyloid (Aβ) peptide accumulation, a hallmark in the pathogenesis of Alzheimer's disease (AD). However, a direct causal relationship between oxidative stress and Aβ 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 β-amyloid precursor protein (APP). Partial deficiency of MnSOD, which is well established to cause elevated oxidative stress, significantly increased brain Aβ levels and Aβ 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.Keywords
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