title: Mitochondrial alterations near amyloid plaques in an Alzheimer's disease mouse model.
abstract: 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. Recent in vitro studies suggested a link between elevated Aβ and mitochondrial dysfunction that might contribute to the pathogenesis of AD. However, the in vivo evidence for mitochondria dysfunction caused by Aβ is still missing. Using intravital multiphoton imaging with a range of fluorescent markers, we systematically surveyed mitochondrial structural and functional changes in AD mouse models. 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. Both neuronal soma and neurites with oxidative stress show severe alterations in mitochondrial membrane potential in amyloid precursor protein mice. These results provide in vivo evidence revealing Aβ plaques as focal sources of toxicity that lead to severe structural and functional abnormalities in mitochondria. These alterations may contribute to neuronal network dysfunction and warrant further investigation as possible targets for therapeutic intervention in AD.
authors.affiliation: MassGeneral Institute for Neurodegenerative Diseases, Massachusetts General Hospital, Charlestown, Massachusetts 02129 and School of Life Sciences, Tsinghua University, 100084 Beijing, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Xie
authors.forename: Jisong
authors.initials: J
authors.lastname: Guan
authors.forename: Laura A
authors.initials: LA
authors.lastname: Borrelli
authors.forename: Jing
authors.initials: J
authors.lastname: Xu
authors.forename: Alberto
authors.initials: A
authors.lastname: Serrano-Pozo
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Bacskai
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism; D000818:Animals; D004195:Disease Models, Animal; D053078:Membrane Potential, Mitochondrial; D051379:Mice; D008822:Mice, Transgenic; D008928:Mitochondria / Q000473:pathology* / Q000502:physiology; D016501:Neurites / Q000378:metabolism / Q000473:pathology; D018384:Oxidative Stress; D058225:Plaque, Amyloid / Q000378:metabolism* / Q000473:pathology
chemical_list: D016564:Amyloid beta-Protein Precursor