Alzheimer’s disease (AD) is a chronic illness marked by increasing cognitive decline and nervous system deterioration. At this time, there is no known medication that will stop the course of Alzheimer’s disease; instead, most symptoms are treated. Clinical trial failure rates for new drugs remain high, highlighting the urgent need for improved AD modeling for improving understanding of the underlying pathophysiology of disease and improving drug development. The development of induced pluripotent stem cells (iPSCs) has made it possible to model neurological diseases like AD, giving access to an infinite number of patient-derived cells capable of differentiating neuronal fates. This advance will accelerate Alzheimer’s disease research and provide an opportunity to create more accurate patient-specific models of Alzheimer’s disease to support pathophysiological research, drug development, and the potential application of stem cell-based therapeutics. This review article provides a complete summary of research done to date on the potential use of iPSCs from AD patients for disease modeling, drug discovery, and cell-based therapeutics. Current technological developments in AD research including 3D modeling, genome editing, gene therapy for AD, and research on familial (FAD) and sporadic (SAD) forms of the disease are discussed. Finally, we outline the issues that need to be elucidated and future directions for iPSC modeling in AD.

中文翻译：

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iPSC 在疾病建模、药物筛选和阿尔茨海默病细胞治疗中的潜在用途

阿尔茨海默病 (AD) 是一种慢性疾病，其特征是认知能力下降和神经系统恶化。目前，还没有已知的药物可以阻止阿尔茨海默病的病程。相反，大多数症状都会得到治疗。新药的临床试验失败率仍然很高，凸显了迫切需要改进 AD 模型，以提高对疾病潜在病理生理学的了解并改进药物开发。诱导多能干细胞 (iPSC) 的发展使得模拟 AD 等神经系统疾病成为可能，从而获得无限数量的能够区分神经元命运的源自患者的细胞。这一进展将加速阿尔茨海默病的研究，并为创建更准确的阿尔茨海默病患者特异性模型提供机会，以支持病理生理学研究、药物开发和干细胞疗法的潜在应用。这篇综述文章完整总结了迄今为止关于 AD 患者 iPSC 在疾病建模、药物发现和基于细胞的治疗中的潜在用途的研究。讨论了 AD 研究的当前技术发展，包括 3D 建模、基因组编辑、AD 基因治疗以及对该疾病的家族性 (FAD) 和散发性 (SAD) 形式的研究。最后，我们概述了 AD 中 iPSC 建模需要阐明的问题和未来方向。