Transmission study of Alzheimer pathology using brain microdialysis

本研究的目的是利用脑微透析技术研究神经元释放到细胞外间隙的可溶性Abeta和tau在阿尔茨海默病病理传递中的可能作用。在初步实验中，通过微透析，我们的tau转基因(TG)小鼠的海马区只检测到非常低水平的tau。为了产生更好的可溶性Abeta和tau供体，我们杂交了我们的APP大阪突变型TG小鼠和野生型tau TG小鼠。双转基因小鼠在6个月时出现Abeta寡聚体积聚、tau过度磷酸化、突触丢失和记忆障碍，18个月时在没有tau突变的情况下出现神经原纤维缠结形成和神经元丢失，所有这些都比亲本转基因小鼠出现得更早。这种小鼠模型将是研究淀粉样蛋白和tau病理的细胞间传播的有用工具。

The purpose of this study is to examine the possible roles of soluble Abeta and tau released from neurons into the extracellular space in the transmission of Alzheimer pathology using the brain microdialysis technique. In a preliminary experiment, only very low levels of tau were detected by microdialysis in the hippocampus of our tau transgenic (Tg) mice. To generate a better donor of soluble Abeta and tau, we crossbred our APP Osaka mutant Tg mice and wild-type tau Tg mice. The resultant double Tg mice showed Abeta oligomer accumulation, tau hyperphosphorylation, synapse loss, and memory impairment at 6 months, and neurofibrillary tangle formation and neuronal loss at 18 months in the absence of tau mutations, all of which appeared earlier than in the parent Tg mice. This mouse model would be a useful tool for investigation of the intercellular propagation of amyloid and tau pathologies.