title: A mouse model of amyloid beta oligomers: their contribution to synaptic alteration, abnormal tau phosphorylation, glial activation, and neuronal loss in vivo.
abstract: Although amyloid beta (Abeta) oligomers are presumed to cause synaptic and cognitive dysfunction in Alzheimer's disease (AD), their contribution to other pathological features of AD remains unclear. To address the latter, we generated APP transgenic mice expressing the E693Delta mutation, which causes AD by enhanced Abeta oligomerization without fibrillization. The mice displayed age-dependent accumulation of intraneuronal Abeta oligomers from 8 months but no extracellular amyloid deposits even at 24 months. Hippocampal synaptic plasticity and memory were impaired at 8 months, at which time the presynaptic marker synaptophysin began to decrease. Furthermore, we detected abnormal tau phosphorylation from 8 months, microglial activation from 12 months, astrocyte activation from 18 months, and neuronal loss at 24 months. These findings suggest that Abeta oligomers cause not only synaptic alteration but also other features of AD pathology and that these mice are a useful model of Abeta oligomer-induced pathology in the absence of amyloid plaques.
authors.affiliation: Departments of Neuroscience, Osaka City University Graduate School of Medicine, Osaka 545-8585, Japan. tomi@med.osaka-cu.ac.jp
authors.forename: Takami
authors.initials: T
authors.lastname: Tomiyama
authors.forename: Shogo
authors.initials: S
authors.lastname: Matsuyama
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Iso
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Umeda
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Takuma
authors.forename: Kiyouhisa
authors.initials: K
authors.lastname: Ohnishi
authors.forename: Kenichi
authors.initials: K
authors.lastname: Ishibashi
authors.forename: Rie
authors.initials: R
authors.lastname: Teraoka
authors.forename: Naomi
authors.initials: N
authors.lastname: Sakama
authors.forename: Takenari
authors.initials: T
authors.lastname: Yamashita
authors.forename: Kazuchika
authors.initials: K
authors.lastname: Nishitsuji
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Ito
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Shimada
authors.forename: Mary P
authors.initials: MP
authors.lastname: Lambert
authors.forename: William L
authors.initials: WL
authors.lastname: Klein
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Mori
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000235:genetics / Q000502:physiology*; D000818:Animals; D016923:Cell Death / Q000235:genetics; D004195:Disease Models, Animal; D006801:Humans; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009457:Neuroglia / Q000378:metabolism* / Q000473:pathology; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D010766:Phosphorylation / Q000235:genetics; D013569:Synapses / Q000378:metabolism* / Q000473:pathology; D016875:tau Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D016229:Amyloid beta-Peptides; D016875:tau Proteins