Isogenic Brain Organoids for Alzheimer’s Disease Research

Isogenic brain organoids are stem-cell-derived three-dimensional brain models designed to control for differences in genetic background while introducing or correcting specific genetic variants. They have emerged as novel model systems for investigating diseases associated with genetic mutations. Alzheimer’s disease (AD), a neurodegenerative disease characterized by progressive cognitive decline and neuronal dysfunction, can be investigated using isogenic brain organoids. This review summarizes recent advances in the development and application of isogenic brain organoids for AD research, focusing on their potential to investigate mutation-specific phenotypes and mechanisms. Limitations associated with clonal variation, differentiation variability, gene-editing effects, and the challenges of translating findings from genetically controlled models to the heterogeneous nature of sporadic AD are also examined. Finally, future directions include improving experimental reproducibility, refining gene-editing strategies, developing more complex disease-relevant models, and evaluating the potential of isogenic organoids for drug screening.