A cell therapy approach to restore microglial Trem2 function in a mouse model of Alzheimer's disease
A cell therapy approach to restore microglial Trem2 function in a mouse model of Alzheimer's disease
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DOI：
10.1016/j.stem.2023.07.006
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发表时间：
2023-08-03
期刊：
影响因子：
23.9
通讯作者：
Wernig, Marius
中科院分区：
文献类型：
--
作者：
Yoo, Yongjin;Neumayer, Gernot;Wernig, Marius
阿尔茨海默病(AD)仍然是人类社会面临的重大挑战之一。关于这种流行疾病的复杂和多方面的发病机制存在着很大的争议。然而，鉴于强有力的人类遗传证据，毫无疑问，小胶质细胞在防止神经元退化方面发挥着重要作用。例如，小胶质细胞基因TREM2的功能丧失会导致小胶质细胞功能障碍，导致早发性神经退行性综合征，而TREM2变异是AD最强烈的遗传风险因素之一。因此，恢复小胶质细胞功能是一种合理的治疗方法。在这里，我们证明了在TREM2突变的AD小鼠模型中，全身造血细胞移植后增强小胶质细胞的替代可以恢复小胶质细胞的功能。
Alzheimer's disease (AD) remains one of the grand challenges facing human society. Much controversy exists around the complex and multifaceted pathogenesis of this prevalent disease. Given strong human genetic evidence, there is little doubt, however, that microglia play an important role in preventing degeneration of neurons. For example, loss of function of the microglial gene Trem2 renders microglia dysfunctional and causes an early-onset neurodegenerative syndrome, and Trem2 variants are among the strongest genetic risk factors for AD. Thus, restoring microglial function represents a rational therapeutic approach. Here, we show that systemic hematopoietic cell transplantation followed by enhancement of microglia replace-ment restores microglial function in a Trem2 mutant mouse model of AD.