Department of Neurodegenerative Diseases, Beckman Research Institute of City of Hope, Duarte, CA 91010, USA; Irell and Manella Graduate School of Biological Sciences, Beckman Research Institute of City of Hope, Duarte, CA 91010, USA.
SciNeuro Pharmaceuticals, Rockville, MD 20850, USA.
Trends Mol Med. 2023 Aug;29(8):659-672. doi: 10.1016/j.molmed.2023.05.007. Epub 2023 Jun 21.
Progression of Alzheimer's disease (AD) entails deterioration or aberrant function of multiple brain cell types, eventually leading to neurodegeneration and cognitive decline. Defining how complex cell-cell interactions become dysregulated in AD requires novel human cell-based in vitro platforms that could recapitulate the intricate cytoarchitecture and cell diversity of the human brain. Brain organoids (BOs) are 3D self-organizing tissues that partially resemble the human brain architecture and can recapitulate AD-relevant pathology. In this review, we highlight the versatile applications of different types of BOs to model AD pathogenesis, including amyloid-β and tau aggregation, neuroinflammation, myelin breakdown, vascular dysfunction, and other phenotypes, as well as to accelerate therapeutic development for AD.
阿尔茨海默病(AD)的进展涉及多种脑细胞类型的恶化或功能异常,最终导致神经退行性变和认知能力下降。定义 AD 中复杂的细胞-细胞相互作用如何失调需要新型的基于人类细胞的体外平台,这些平台可以再现人类大脑的复杂细胞结构和细胞多样性。脑类器官(BOs)是 3D 自组织组织,部分类似于人类大脑结构,可以再现与 AD 相关的病理学。在这篇综述中,我们强调了不同类型的 BOs 在模拟 AD 发病机制方面的多种应用,包括淀粉样蛋白-β和 tau 聚集、神经炎症、髓鞘破坏、血管功能障碍和其他表型,以及加速 AD 的治疗开发。
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