Modeling Alzheimer's disease using cerebral organoids: Current challenges and prospects

“Brain organoids”, “cerebral organoids” or “mini-brains” are the terms that have been frequently used to describe self-organizing 3D structures which could be derived from embryonic stem cells (ESCs), adult stem cells, or induced pluripotent stem cells (iPSCs). The fact that certain cell types could be reprogrammed to study some aspects of brain development and certain disease conditions has advanced our understanding of brain development in health and disease. Human brain development is somewhat intriguing, however, complex, sharing close similarities with both primate and rodent brain development, despite species heterogeneity. The in-vivo and in-vitro models have been used over time to study the development of the brain in health and disease states. The in-vitro system being a monolayer system is unable to recapitulate some essential aspects of human brain development and even certain disease conditions like microcephaly, Alzheimer's disease (AD), and Frontotemporal dementia (FTD) to mention a few, because of the complex pathophysiology of these diseases. Based on this premise, recent studies are now beginning to examine the role of patient-derived human tissues reprogrammed into stem cells with the ability to organize into 3D cerebral organoids in studying and understanding the complex nature of neurodegenerative diseases which have been difficult to model in-vitro and in-vivo. Here, we highlight evidence of patient-derived brain organoids in modeling Alzheimer’s disease, providing evidence on the current challenges and prospects in growing cerebral organoids and some approaches that have been developed to overcome these challenges.