神经退行性疾病是成年发病的神经系统疾病，由于大多数模型不能准确重现与疾病相关的细胞病理，导致在药物研发领域中很难找到有效的模型，进而难以探索神经退行性疾病的潜在机制。因此，为了弥补这一差距并更准确地预测新治疗策略的影响，研究人员开发了人类或动物细胞的替代模型，试图模拟神经元和胶质细胞的相互作用以及其他多种机制。伴随着2007年首次成功生成人工诱导多能干细胞（hiPSC）的突破，如今可以获得从患者派生的hiPSC，通过将其分化为与疾病相关的神经元，为体外模拟、药物测试和治疗策略开发提供了一个无与伦比的平台。最近，从iPSC衍生的三维（3D）脑器官样体作为研究神经退行性疾病病理特征的最佳替代模型得到了广泛发展。本综述回顾了当前基于iPSC的疾病模型及其在神经退行性疾病模型中的最新进展。此外，还概述了基于脑器官样体的阿尔茨海默病模型的研究现状。我们还讨论了区域特异性脑器官样体建模的当前方法，以其潜在应用为重点，强调脑器官样体作为模拟特定患者疾病、发展个体化治疗并对器官样体技术进行进行进行进行进行进入进行临床试验的设计方面有着巨大的潜力。版权所有© 2023 Jusop, Thanaskody, Tye, Dass, Wan Kamarul Zaman和Nordin。

Neurodegenerative diseases are adult-onset neurological conditions that are notoriously difficult to model for drug discovery and development because most models are unable to accurately recapitulate pathology in disease-relevant cells, making it extremely difficult to explore the potential mechanisms underlying neurodegenerative diseases. Therefore, alternative models of human or animal cells have been developed to bridge the gap and allow the impact of new therapeutic strategies to be anticipated more accurately by trying to mimic neuronal and glial cell interactions and many more mechanisms. In tandem with the emergence of human-induced pluripotent stem cells which were first generated in 2007, the accessibility to human-induced pluripotent stem cells (hiPSC) derived from patients can be differentiated into disease-relevant neurons, providing an unrivaled platform for in vitro modeling, drug testing, and therapeutic strategy development. The recent development of three-dimensional (3D) brain organoids derived from iPSCs as the best alternative models for the study of the pathological features of neurodegenerative diseases. This review highlights the overview of current iPSC-based disease modeling and recent advances in the development of iPSC models that incorporate neurodegenerative diseases. In addition, a summary of the existing brain organoid-based disease modeling of Alzheimer's disease was presented. We have also discussed the current methodologies of regional specific brain organoids modeled, its potential applications, emphasizing brain organoids as a promising platform for the modeling of patient-specific diseases, the development of personalized therapies, and contributing to the design of ongoing or future clinical trials on organoid technologies.Copyright © 2023 Jusop, Thanaskody, Tye, Dass, Wan Kamarul Zaman and Nordin.