Alzheimer's disease (AD) is a progressive, neurodegenerative disease that has emerged as a leading risk factor for dementia associated with increasing age. Two-dimensional (2D) cell culture and animal models, which have been used to analyze AD pathology and search for effective treatments for decades, have significantly contributed to our understanding of the mechanism of AD. Despite their successes, 2D and animal models can only capture a fraction of AD mechanisms due to their inability to recapitulate human brain-specific tissue structure, function, and cellular diversity. Recently, the emergence of three-dimensional (3D) cerebral organoids using tissue engineering and induced pluripotent stem cell technology has paved the way to develop models that resemble features of human brain tissue more accurately in comparison to prior models. In this review, we focus on summarizing key research strategies for engineering in vitro 3D human brain-specific models, major discoveries from using AD cerebral organoids, and its future perspectives.

中文翻译：

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模拟阿尔茨海默病起源和机制的脑类器官的最新进展

阿尔茨海默病 (AD) 是一种进行性神经退行性疾病，已成为与年龄增长相关的痴呆症的主要危险因素。二维（2D）细胞培养和动物模型几十年来一直用于分析 AD 病理学和寻找有效的治疗方法，为我们对 AD 机制的理解做出了重大贡献。尽管取得了成功，但二维和动物模型只能捕获 AD 机制的一小部分，因为它们无法重现人脑特定的组织结构、功能和细胞多样性。最近，使用组织工程和诱导多能干细胞技术的三维 (3D) 大脑类器官的出现，为开发比以前的模型更准确地模拟人类脑组织特征的模型铺平了道路。在这篇综述中，我们重点总结了体外 3D 人脑特异性模型工程的关键研究策略、使用 AD 大脑类器官的主要发现及其未来前景。