Pikus Philip, Turner R Scott, Rebeck G William
Department of Neuroscience, Georgetown University Medical Center, 3970 Reservoir Rd, NW, District of Columbia, Washington, 20007, USA.
Interdisciplinary Program in Neuroscience, Georgetown University, 3970 Reservoir Rd, NW, District of Columbia, Washington, 20007, USA.
Mol Neurodegener. 2025 May 13;20(1):57. doi: 10.1186/s13024-025-00836-x.
The development of anti-amyloid-beta (Aβ) immunotherapies as the first disease modifying therapy for Alzheimer's Disease (AD) is a breakthrough of basic research and translational science.
Genetically modified mouse models developed to study AD neuropathology and physiology were used for the discovery of Aβ immunotherapies and helped ultimately propel therapies to FDA approval. Nonetheless, the combination of modest efficacy and significant rates of an adverse side effect (amyloid related imaging abnormalities, ARIA), has prompted reverse translational research in these same mouse models to better understand the mechanism of the therapies.
This review considers the use of these mouse models in understanding the mechanisms of Aβ clearance, cerebral amyloid angiopathy (CAA), blood brain barrier breakdown, neuroinflammation, and neuronal dysfunction in response to Aβ immunotherapy.
抗淀粉样β蛋白（Aβ）免疫疗法作为阿尔茨海默病（AD）的首个疾病修饰疗法的研发，是基础研究和转化科学的一项突破。
为研究AD神经病理学和生理学而开发的转基因小鼠模型被用于Aβ免疫疗法的发现，并最终推动这些疗法获得美国食品药品监督管理局（FDA）的批准。尽管如此，疗效一般与不良副作用（淀粉样蛋白相关成像异常，ARIA）发生率较高的情况相结合，促使在这些相同的小鼠模型中开展反向转化研究，以更好地理解这些疗法的机制。
本综述探讨了利用这些小鼠模型来理解Aβ清除、脑淀粉样血管病（CAA）、血脑屏障破坏、神经炎症以及Aβ免疫疗法引发的神经元功能障碍的机制。
