Overexpression of SOD-2 reduces hippocampal superoxide and prevents memory deficits in a mouse model of Alzheimer's disease

Cynthia A. Massaad, Taneasha M. Washington, Robia G. Pautler, Eric Klann

Research output: Contribution to journalArticlepeer-review

Abstract

Alzheimer's disease (AD) is a neurodegenerative disease characterized by impaired cognitive function and the deposition of extracellular amyloid plaques and intracellular tangles. Although the proximal cause of AD is not well understood, it is clear that amyloid-β(Aβ) plays a critical role in AD pathology. Recent studies also implicate mitochondrial abnormalities in AD. We investigated this idea by crossing mice that overexpress mitochondrial superoxide dismutase (SOD-2) with the Tg2576 mouse model of AD that overexpresses the human amyloid precursor protein carrying the Swedish mutation (K670N:M671L). We found that overexpression of SOD-2 decreased hippocampal superoxide, prevented AD-related learning and memory deficits, and reduced Aβ plaques. Interestingly, SOD-2 overexpression did not affect the absolute levels of Aβ1-40 and Aβ1-42, but did significantly reduce the Aβ1-42 to Aβ1-40 ratio, thereby shifting the balance toward a less amyloidogenic Aβ composition. These findings directly link mitochondrial superoxide to AD pathology and demonstrate the beneficial effects of a mitochondrial anti-oxidant enzyme, hence offering significant therapeutic implications for AD.

Original languageEnglish (US)
Pages (from-to)13576-13581
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume106
Issue number32
DOIs
StatePublished - Aug 11 2009

Keywords

  • Antioxidant
  • Dementia
  • Mitochondria
  • Oxidative stress
  • Reactive oxygen species

ASJC Scopus subject areas

  • General

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