Increased plaque burden in brains of APP mutant MnSOD heterozygous knockout mice Academic Article uri icon


MeSH Major

  • Alzheimer Disease
  • Amyloid beta-Peptides
  • Amyloid beta-Protein Precursor
  • Brain
  • Plaque, Amyloid
  • Superoxide Dismutase


  • 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.

publication date

  • June 2004



  • Academic Article



  • eng

Digital Object Identifier (DOI)

  • 10.1111/j.1471-4159.2004.02455.x

PubMed ID

  • 15147524

Additional Document Info

start page

  • 1308

end page

  • 12


  • 89


  • 5