Characterization of Alzheimer’s disease transgenic animal model by Aβ, Tau and neuroinflammation PET tracers

Introduction: The two most obvious pathological features of Alzheimer disease (AD) are Aβ plaque and neurofibrillary tangle (NFT). Now it is found that the genes closely related to AD include APP, PSI, PSII, ApoE and so on. In view of these genes, transgenic mice were developed to simulate the clinical and pathological conditions and provide useful models for research. In this study, we selected triple transgenic AD mice, which were classical model for studying amyloid deposition, tau pathology and synaptic transmission. These mice expressing three mutant genes: Psen1 M146V, APPSwe and Tau P301L. In recent years, researchers have developed a variety of PET tracers for different targets of Alzheimer's disease. Few studies identified the same model by different PET tracers. Methods: In this study, we used the B6;129-Psen1tm1Mpm Tg(APPSwe,tauP301L)1Lfa/Mmjax mouse model, which was confirmed by RT-PCR and behavior test. ¹⁸F-AV45, ¹⁸F-PM-PBB3 and ¹⁸F-DPA714 was synthesized by the previously reported. Serial microPET was used to investigate the uptake of tracer in the AD transgenic mice and control at different ages. Results: We have proved the successful establishment of transgenic models by RT-PCR and behavior tests. By ¹⁸F-AV45 PET imaging, we found that the radioactive uptake is relative higher in brain of transgenic mice compared with control group. We observed more serious tau fibrosis in the same model by ¹⁸F-PM-PBB3 PET imaging. We also confirmed the hyper-activation of microglia in model by ¹⁸F-DPA714, a specific tracer of translocate protein of activated microglia. Conclusion: In summary, we demonstrate that combination of different PET tracers can be used to identify triple-transgenic animal models in vivo. The ¹⁸F-AV45 and ¹⁸F-PM-PBB3 tracers used correspond to the APPSwe gene and tauP310L gene respectively, so that we can understand the pathophysiological process of the model in multiple dimensions. Acknowledgments :This study was supported by the National Natural Science Foundation of China (Project No. 81571345, 81701732), National Key Research and Development Program Foundation of China(No: 2016YFC1306403), National Key Research and Development Program Foundation of China(No: 2016YFC1306403), Natural Science Foundation and Major Basic Research Program of Shanghai(No: 16JC1420100), Natural Science Foundation and Major Basic Research Program of Shanghai(No: 16JC1420502).No other potential conflicts of interest relevant to this article exist.