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 journalArticle

21 Citations (Scopus)

Abstract

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
Pages (from-to)2399-2407
Number of pages9
JournalNeurobiology of Aging
Volume34
Issue number10
DOIs
StatePublished - Oct 1 2013

Fingerprint

Amyloid Plaques
Mitochondrial DNA
DNA Damage
Alzheimer Disease
Reactive Oxygen Species
Pathology
Amyloid beta-Protein Precursor
Oxidative Phosphorylation
Amyloid
Oxidative Stress
Central Nervous System
Neurons
Brain

Keywords

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

ASJC Scopus subject areas

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

Cite this

Mitochondrial DNA damage in a mouse model of alzheimer's disease decreases amyloid beta plaque formation. / Pinto, Milena; Pickrell, Alicia M.; Fukui, Hirokazu; Moraes, Carlos T.

In: Neurobiology of Aging, Vol. 34, No. 10, 01.10.2013, p. 2399-2407.

Research output: Contribution to journalArticle

Pinto, Milena ; Pickrell, Alicia M. ; Fukui, Hirokazu ; Moraes, Carlos T. / Mitochondrial DNA damage in a mouse model of alzheimer's disease decreases amyloid beta plaque formation. In: Neurobiology of Aging. 2013 ; Vol. 34, No. 10. pp. 2399-2407.
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