A mouse model of amyloid beta oligomers: their contribution to synaptic alteration, abnormal tau phosphorylation, glial activation, and neuronal loss in vivo
| Autor: | Hiroyuki Iso, Kiyouhisa Ohnishi, Hiroshi Takuma, Hiroshi Mori, Takami Tomiyama, Hiroyuki Shimada, Rie Teraoka, Mary P. Lambert, Kazuchika Nishitsuji, Shogo Matsuyama, Takenari Yamashita, Kenichi Ishibashi, Naomi Sakama, Tomohiro Umeda, Kazuhiro Ito, William L. Klein |
|---|---|
| Rok vydání: | 2010 |
| Předmět: |
Genetically modified mouse
Male Amyloid Transgene Mice Transgenic tau Proteins medicine.disease_cause Mice Alzheimer Disease medicine Extracellular Animals Humans Phosphorylation Neurons Mutation Mice Inbred C3H Amyloid beta-Peptides biology Cell Death General Neuroscience P3 peptide Articles Cell biology Mice Inbred C57BL Disease Models Animal medicine.anatomical_structure Synapses Synaptophysin biology.protein Neuroscience Neuroglia Astrocyte |
| Zdroj: | The Journal of neuroscience : the official journal of the Society for Neuroscience. 30(14) |
| ISSN: | 1529-2401 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|