iPSC-derived neural organoids in dementia research: Recent advances and future directions

Neural organoids are self-assembled three-dimensionally shaped aggregates generated from pluripotent stem cells for the purpose of generating brain-like structures. The features of the disease, from molecular to functional levels, can be recapitulated by neural organoids derived from patient induced pluripotent stem cells (iPSCs). These features are not fully reproduced by other culture systems or in vivo models. Neural organoids have been applied to model dementia including Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis/frontotemporal dementia, and they have recapitulated aspects of their complex pathophysiology, including neuronal network dysfunction and accumulation of pathogenic proteins. Although research using neural organoids still faces challenges such as heterogeneity and the absence of non-neural lineage cells, these limitations are being progressively addressed. Recent advances, including the integration of gene-editing technologies and the co-assembly of organoids with specific cell types, have demonstrated the remarkable potential of this approach. This article reviews current research on iPSC-derived neural organoids for dementia, discussing both the technical hurdles and the potential for translational applications.