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Mitochondrial dysfunction in a transgenic mouse model expressing human amyloid precursor protein ( APP ) with the Arctic mutation
Author(s) -
Rönnbäck Annica,
Pavlov Pavel. F.,
Mansory Mansorah,
Gonze Prisca,
Marlière Nicolas,
Winblad Bengt,
Graff Caroline,
Behbahani Homira
Publication year - 2016
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/jnc.13410
Subject(s) - amyloid precursor protein , mitochondrial dna , genetically modified mouse , mitochondrion , oxidative stress , mutation , biology , reactive oxygen species , amyloid (mycology) , transgene , alzheimer's disease , microbiology and biotechnology , endocrinology , medicine , biochemistry , gene , disease , botany
Accumulation of amyloid β‐peptide (Aβ) in the brain is an important event in the pathogenesis of Alzheimer disease. We have used a transgenic mouse model expressing human amyloid precursor protein ( APP ) with the Arctic mutation to investigate whether Aβ deposition is correlated with mitochondrial functions in these animals. We found evidence of mitochondrial dysfunction (i.e., decreased mitochondrial membrane potential, increased production of reactive oxygen species and oxidative DNA damage) at 6 months of age, when the mice showed very mild Aβ deposition. More pronounced mitochondrial abnormalities were present in 24‐month‐old Tg APP arc mice with more extensive Aβ pathology. This study demonstrates for the first time mitochondrial dysfunction in transgenic mice with a mutation within the Aβ peptide (the Arctic APP mutation), and confirms previous studies suggesting that mitochondrial dysfunction and oxidative stress is an early event in the pathogenesis of Alzheimer disease.This study demonstrates mitochondrial dysfunction in transgenic mice with a mutation within the amyloid beta (Aβ) peptide (the Arctic amyloid precursor protein (APP) mutation). We found evidence of mitochondrial dysfunction (i.e. decreased mitochondrial membrane potential (MMP), increased production of reactive oxygen species (ROS) and oxidative DNA damage) at 6 months of age, when very mild Aβ deposition is present in the mice. Also, the cytochrome c (COX) activity was significantly decreased in mitochondria from transgenic mice at 24 months of age.