A mouse model of amyloid β oligomers: Their contribution to synaptic alteration, abnormal tau phosphorylation, glial activation, and neuronal loss in vivo

Takami Tomiyama*, Shogo Matsuyama, Hiroyuki Iso, Tomohiro Umeda, Hiroshi Takuma, Kiyouhisa Ohnishi, Kenichi Ishibashi, Rie Teraoka, Naomi Sakama, Takenari Yamashita, Kazuchika Nishitsuji, Kazuhiro Ito, Hiroyuki Shimada, Mary P. Lambert, William L. Klein, Hiroshi Mori

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

270 Scopus citations

Abstract

Although amyloid β (Aβ) 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 E693Δ mutation, which causes AD by enhanced Aβ oligomerization without fibrillization. The mice displayed age-dependent accumulation of intraneuronal Aβ 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 Aβ oligomers cause not only synaptic alteration but also other features of AD pathology and that these mice are a useful model of Aβ oligomer-induced pathology in the absence of amyloid plaques.

Original languageEnglish (US)
Pages (from-to)4845-4856
Number of pages12
JournalJournal of Neuroscience
Volume30
Issue number14
DOIs
StatePublished - Apr 7 2010

ASJC Scopus subject areas

  • Neuroscience(all)

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