| First Author | Ochiishi T | Year | 2019 |
| Journal | Sci Rep | Volume | 9 |
| Issue | 1 | Pages | 17368 |
| PubMed ID | 31757975 | Mgi Jnum | J:287166 |
| Mgi Id | MGI:6405942 | Doi | 10.1038/s41598-019-53415-8 |
| Citation | Ochiishi T, et al. (2019) New Alzheimer's disease model mouse specialized for analyzing the function and toxicity of intraneuronal Amyloid beta oligomers. Sci Rep 9(1):17368 |
| abstractText | Oligomers of intracellular amyloid beta protein (Abeta) are strongly cytotoxic and play crucial roles in synaptic transmission and cognitive function in Alzheimer's disease (AD). However, there is currently no AD model mouse in which to specifically analyze the function of Abeta oligomers only. We have now developed a novel AD model mouse, an Abeta-GFP transgenic mouse (Abeta-GFP Tg), that expresses the GFP-fused human Abeta1-42 protein, which forms only Abeta oligomers within neurons throughout their life. The fusion proteins are expressed mainly in the hippocampal CA1-CA2 region and cerebral cortex, and are not secreted extracellularly. The Abeta-GFP Tg mice exhibit increased tau phosphorylation, altered spine morphology, decreased expressions of the GluN2B receptor and neuroligin in synaptic regions, attenuated hippocampal long-term potentiation, and impaired object recognition memory compared with non-Tg littermates. Interestingly, these dysfunctions have already appeared in 2-3-months-old animals. The Abeta-GFP fusion protein is bioactive and highly toxic, and induces the similar synaptic dysfunctions as the naturally generated Abeta oligomer derived from postmortem AD patient brains and synthetic Abeta oligomers. Thus, Abeta-GFP Tg mouse is a new tool specialized to analyze the function of Abeta oligomers in vivo and to find subtle changes in synapses in early symptoms of AD. |
