Gas6 improves plaque burden, yet worsens behavior and induces microglial inflammation in the APP/PS1 model of Alzheimer's disease

We sought to determine the effects of Gas6 on Alzheimer's disease pathology through overexpression of Gas6 using an adeno-associated viral vector in the APP/PS1 model of Alzheimer's disease. 9 month old male and female APP/PS1 and nontransgenic littermates received bilateral stereotactic hippocampal injections of AAV-Gas6 or AAV-control, an attenuated Gas6 protein that does not bind the Axl receptor. One month after injections, mice performed a battery of behavioral tasks and brains were processed for immunohistochemistry, transcriptional analyses, and flow cytometry. Overall design: Microglia (CD45int CD11b+) were sorted from isolated hippocampi and processed for RNAseq.

本研究旨在通过在APP/PS1阿尔茨海默病模型中利用腺相关病毒载体（adeno-associated viral vector, AAV）过表达Gas6，探究Gas6对阿尔茨海默病病理进程的影响。选取9月龄的雌雄APP/PS1小鼠及非转基因同窝仔鼠，对其实施双侧立体定位海马注射，注射试剂分为AAV-Gas6与AAV-对照，其中AAV-对照携带无法结合Axl受体的减毒Gas6蛋白。注射后1个月，对小鼠开展一系列行为学测试，随后取脑组织进行免疫组织化学检测、转录组分析及流式细胞术检测。实验整体设计：从分离的海马组织中分选CD45int CD11b+小胶质细胞，并进行RNAseq测序。