Mitochondrial dysfunction is an attractive hypothesis for the pathogenesis of Alzheimer's disease (AD) and aging-related senile dementia ( Smith et al., 1996 Fukui and Moraes, 2008 Mattson et al., 2008). These alterations may contribute to neuronal network dysfunction and warrant further investigation as possible targets for therapeutic intervention in AD. These results provide in vivo evidence revealing Aβ plaques as focal sources of toxicity that lead to severe structural and functional abnormalities in mitochondria. Both neuronal soma and neurites with oxidative stress show severe alterations in mitochondrial membrane potential in amyloid precursor protein mice. We observed severe impairments to be limited to the vicinity of Aβ plaques, which included reduction of both numbers and membrane potential of mitochondria and the emergence of dystrophic and fragmented mitochondria.
Using intravital multiphoton imaging with a range of fluorescent markers, we systematically surveyed mitochondrial structural and functional changes in AD mouse models. However, the in vivo evidence for mitochondria dysfunction caused by Aβ is still missing. Recent in vitro studies suggested a link between elevated Aβ and mitochondrial dysfunction that might contribute to the pathogenesis of AD. While accumulation of amyloid-β (Aβ) deposited as senile plaques is a hallmark feature of Alzheimer's disease (AD), the neurotoxicity of these deposits remains controversial.
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