Mitochondrial DNA damage in a mouse model of alzheimer's disease decreases amyloid beta plaque formation

Milena Pinto, Alicia M. Pickrell, Hirokazu Fukui, Carlos T. Moraes

Research output: Contribution to journalArticlepeer-review

27 Scopus citations


Mitochondrial DNA (mtDNA) damage and the generation of reactive oxygen species have been associated with and implicated in the development and progression of Alzheimer's disease. To study how mtDNA damage affects reactive oxygen species and amyloid beta (Aβ) pathology invivo, we generated an Alzheimer's disease mouse model expressing an inducible mitochondrial-targeted endonuclease (Mito-. PstI) in the central nervous system. Mito-. PstI cleaves mtDNA causing mostly an mtDNA depletion, which leads to a partial oxidative phosphorylation defect when expressed during a short period in adulthood. We found that a mild mitochondrial dysfunction in adult neurons did not exacerbate Aβ accumulation and decreased plaque pathology. Mito-. PstI expression altered the cleavage pathway of amyloid precursor protein without increasing oxidative stress in the brain. These data suggest that mtDNA damage is not a primary cause of Aβ accumulation.

Original languageEnglish (US)
Pages (from-to)2399-2407
Number of pages9
JournalNeurobiology of aging
Issue number10
StatePublished - Oct 2013


  • Alzheimer
  • APP cleavage
  • mtDNA damage
  • Plaque formation
  • ROS

ASJC Scopus subject areas

  • Clinical Neurology
  • Neuroscience(all)
  • Aging
  • Developmental Biology
  • Geriatrics and Gerontology


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