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. Microglia (CD45int CD11b+) were sorted from isolated hippocampi and processed for RNAseq.