源自年轻野生型小鼠的脾细胞可预防APPswe/PSEN1dE9转基因小鼠的阿尔茨海默病进展。

Splenocytes derived from young WT mice prevent AD progression in APPswe/PSENldE9 transgenic mice.

作者信息

Wang Fei, Shen Xueyan, Li Shuping, Chen Long, Wang Yanru, Qin Jie, Zhou Guomin, Peng Yuwen, Feng Xiaoyuan, Li Ruixi, Liang Chunmin

机构信息

Department of Anatomy and Histology & Embryology, Shanghai Medical College of Fudan University, Shanghai, P. R. China.

Department of Radiology, Huashan Hospital, Fudan University, Shanghai, P. R. China.

出版信息

Oncotarget. 2015 Aug 28;6(25):20851-62. doi: 10.18632/oncotarget.4930.

Immunosenescence contributes to pathogenesis of Alzheimer's disease (AD) in the elderly. In this study, we explored the effects of young wild type (WT) splenocytes (ySCs) on Alzheimer's disease by transplanting ySCs into APPswe/PSENldE9 transgenic mice. Young WT splenocytes not only prevented AD, but also improved the spatial learning and memory of APPswe/PSENldE9 transgenic mice. Young WT splenocytes enhanced Aβ clearance, decreased astrogliosis and increased systemic growth differentiation factor 11 (GDF11) levels. Splenocytes derived from old AD mouse promoted AD. There was an increased number of regulatory T cells (Tregs) among old AD splenocytes. We suggest that alterations of GDF11 and Tregs are involved in AD progression and that rejuvenation of the immune system is a potential therapeutic strategy in AD.

免疫衰老促成了老年人阿尔茨海默病（AD）的发病机制。在本研究中，我们通过将年轻野生型（WT）脾细胞（ySCs）移植到APPswe/PSENldE9转基因小鼠体内，探讨了ySCs对阿尔茨海默病的影响。年轻WT脾细胞不仅预防了AD，还改善了APPswe/PSENldE9转基因小鼠的空间学习和记忆能力。年轻WT脾细胞增强了Aβ清除，减少了星形胶质细胞增生，并提高了全身生长分化因子11（GDF11）水平。来自老年AD小鼠的脾细胞促进了AD。老年AD脾细胞中调节性T细胞（Tregs）数量增加。我们认为，GDF11和Tregs的改变参与了AD的进展，免疫系统的年轻化是AD的一种潜在治疗策略。