Neuroscience Institute, NYU Grossman School of Medicine, New York, NY 10016, USA.
Department of Neuroscience and Physiology, NYU Grossman School of Medicine, New York, NY 10016, USA.
Cells. 2020 Nov 4;9(11):2415. doi: 10.3390/cells9112415.
Alzheimer's disease (AD) is the most common form of dementia. Despite many years of intense research, there is currently still no effective treatment. Multiple cell types contribute to disease pathogenesis, with an increasing body of data pointing to the active participation of astrocytes. Astrocytes play a pivotal role in the physiology and metabolic functions of neurons and other cells in the central nervous system. Because of their interactions with other cell types, astrocyte functions must be understood in their biologic context, thus many studies have used mouse models, of which there are over 190 available for AD research. However, none appear able to fully recapitulate the many functional changes in astrocytes reported in human AD brains. Our review summarizes the observations of astrocyte biology noted in mouse models of familial and sporadic AD. The limitations of AD mouse models will be discussed and current attempts to overcome these disadvantages will be described. With increasing understanding of the non-neuronal contributions to disease, the development of new methods and models will provide further insights and address important questions regarding the roles of astrocytes and other non-neuronal cells in AD pathophysiology. The next decade will prove to be full of exciting opportunities to address this devastating disease.
阿尔茨海默病（AD）是最常见的痴呆症形式。尽管经过多年的深入研究，但目前仍然没有有效的治疗方法。多种细胞类型参与疾病的发病机制，越来越多的数据表明星形胶质细胞的积极参与。星形胶质细胞在神经元和中枢神经系统中其他细胞的生理和代谢功能中起着关键作用。由于它们与其他细胞类型的相互作用，必须在其生物学背景下理解星形胶质细胞的功能，因此许多研究使用了超过 190 种用于 AD 研究的小鼠模型。然而，没有一种模型似乎能够完全再现人类 AD 大脑中报告的星形胶质细胞的许多功能变化。我们的综述总结了在家族性和散发性 AD 小鼠模型中观察到的星形胶质细胞生物学的观察结果。将讨论 AD 小鼠模型的局限性，并描述目前克服这些缺点的尝试。随着对非神经元对疾病的贡献的理解不断增加，新方法和模型的发展将提供进一步的见解，并解决星形胶质细胞和其他非神经元细胞在 AD 病理生理学中的作用的重要问题。接下来的十年将充满令人兴奋的机会，以解决这一破坏性疾病。
