Advantages and limitations of hiPSC-derived neurons for the study of neurodegeneration

Neurodegenerative diseases, such as Alzheimer's disease (AD), are expensive, common, and will likely increase as the population ages. The lack of significant therapeutic development indicates that further research is needed on various cellular mechanisms that contribute to neurodegeneration. Human-induced pluripotent stem cell (hiPSC) technology has provided living, dynamic cellular models to address this challenge. Here, we discuss these models in the context of AD and related dementias and review the insights these models have made into disease mechanisms. We include discussion of genetic forms of AD and strong AD risk factors and discuss how these are modeled in both two-dimensional cultures and three-dimensional cerebral organoids. We address the limitations of the system, in particular how to incorporate brain aging, and we summarize drug discovery efforts using hiPSC-derived neurons.