Mouse induced pluripotent stem cells-derived Alzheimer's disease cerebral organoid culture and neural differentiation disorders

摘要

Alzheimer's disease (AD) is a progressive neurodegenerative disease, characterized by cognitive impairment. However, the pathogenesis of AD are very complicated, and the theories of A beta and neurofibrillary tangles cannot explain all pathological alterations and clinical symptoms. Here, we used three-dimensional (3D) neural organoids culture derived from mouse induced pluripotent stem cells (iPSCs) to investigate the pathological mechanisms of AD. In this study, AD cerebral organoids were generated by overexpressing familial AD mutations (APP and PS1 genes) in mouse induced pluripotent stem cells, so that the early pathogenesis of AD could be investigated well with protein and cellular phenotype analyses. The results showed that AD cerebral organoids appeared some AD pathological alterations, and high levels of A beta and p-Tau were induced as well. Furthermore, the number of GFAP-positive astrocytes and glutamatergic excitatory neurons increased significantly, but the number of GABAergic interneurons decreased. In conclusion, we suggest that cerebral organoids are a suitable AD model for scientific study, and that will provide us a novel insight into the understanding of the pathogenesis of AD.