Preliminary Behavioral, Pathological and Transcriptome Studies of Tree Shrew: Evidence for a Complementary Small-Animal Alzheimer's Disease Model

Most small-animal studies of Alzheimer's disease (AD) involve rats and mice, yet the tree shrew (Tupaia belangeri) is in many respects more similar to primates than rodents are. To demonstrate the feasibility and usefulness of using the tree shrew as an AD model, we examined how well the model recapitulates features of the disease. Injecting animals intraperitoneally with D-galactose to induce acute senility, and then injecting them with beta amyloid fragment 1-42 and ibotenic acid into the bilateral hippocampus led to significant learning and memory deficits in the Morris water maze test. Pathology analysis of treated animals showed obvious gliosis and neurofibrillary tangles in the cerebral hippocampal area. These results suggest that the tree shrew can recapitulate the major features of AD pathogenesis. To provide the basis for further studies with this new animal model, we used high-throughput sequencing to analyze changes in the hippocampal transcriptome induced by injection of the three AD agents. These results open the door to new small-animal studies of AD that complement and extend studies in rodents and primates.