TY - JOUR T1 - A Mouse Model of Amyloid β Oligomers: Their Contribution to Synaptic Alteration, Abnormal Tau Phosphorylation, Glial Activation, and Neuronal Loss <em>In Vivo</em> JF - The Journal of Neuroscience JO - J. Neurosci. SP - 4845 LP - 4856 DO - 10.1523/JNEUROSCI.5825-09.2010 VL - 30 IS - 14 AU - Takami Tomiyama AU - Shogo Matsuyama AU - Hiroyuki Iso AU - Tomohiro Umeda AU - Hiroshi Takuma AU - Kiyouhisa Ohnishi AU - Kenichi Ishibashi AU - Rie Teraoka AU - Naomi Sakama AU - Takenari Yamashita AU - Kazuchika Nishitsuji AU - Kazuhiro Ito AU - Hiroyuki Shimada AU - Mary P. Lambert AU - William L. Klein AU - Hiroshi Mori Y1 - 2010/04/07 UR - http://www.jneurosci.org/content/30/14/4845.abstract N2 - 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. ER -