Curr Opin Neurobiol. 2022 Feb;72:120-130. doi: 10.1016/j.conb.2021.10.003. Epub 2021 Nov 21.
Alzheimer's disease (AD) is a devastating neurodegenerative disorder affecting the aging population. Despite many studies, there remains an urgent need to identify the root causes of AD, together with potential treatments. Cerebral organoid technology has made it possible to model human neurophysiology and disease with increasing accuracy in patient-derived tissue cultures. Here, we review the most recent advances in modeling AD in organoids and other engineered three-dimensional cell culture systems. Early studies demonstrated that familial AD patient-derived organoids robustly develop disease pathology. Ongoing work has expanded this focus to investigate the genetic and environmental causes of late-onset sporadic AD and harness organoids for high-throughput drug screens. Future organoid models will need to incorporate additional cell types and tissues implicated in disease pathogenesis, including microglia and vasculature. We anticipate the continuation of this rapid progress in developing cerebral organoid technology toward facilitating our understanding of and informing treatment strategies for AD.
阿尔茨海默病（AD）是一种严重的神经退行性疾病，影响着老年人群体。尽管进行了许多研究，但仍迫切需要确定 AD 的根本原因以及潜在的治疗方法。类脑器官技术使得在患者来源的组织培养物中越来越精确地模拟人类神经生理学和疾病成为可能。在这里，我们回顾了在类器官和其他工程化三维细胞培养系统中模拟 AD 的最新进展。早期研究表明，家族性 AD 患者来源的类器官会强烈地发展出疾病病理学。正在进行的工作已经将这一重点扩展到研究散发性迟发性 AD 的遗传和环境原因，并利用类器官进行高通量药物筛选。未来的类器官模型将需要纳入更多与疾病发病机制相关的细胞类型和组织，包括小胶质细胞和血管系统。我们预计，开发类脑器官技术的这一快速进展将继续下去，以帮助我们理解 AD 并为其治疗策略提供信息。
