Rejuvenation of peripheral immune cells attenuates Alzheimer’s disease-like pathologies and behavioral deficits in a mouse model
Pu‐Yang Sun, Jie Liu, Jian-Ni Hu, Yun‐Feng Tu, Qiu Jiang, Yujuan Jia, Hao‐Lun Sun, Si-Han Chen, Jiayan Xin, Zhongyuan Yu, Zhihao Liu, Cheng‐Rong Tan, Gui‐Hua Zeng, An‐Yu Shi, Yuhui Liu, Xian‐Le Bu, Yan‐Jiang Wang, Jun Wang
Abstract
Immunosenescence contributes to systematic aging and plays a role in the pathogenesis of Alzheimer’s disease (AD). Therefore, the objective of this study was to investigate the potential of immune rejuvenation as a therapeutic strategy for AD. To achieve this, the immune systems of aged APP/PS1 mice were rejuvenated through young bone marrow transplantation (BMT). Single-cell RNA sequencing revealed that young BMT restored the expression of aging- and AD-related genes in multiple cell types within blood immune cells. The level of circulating senescence-associated secretory phenotype proteins was decreased following young BMT. Notably, young BMT resulted in a significant reduction in cerebral Aβ plaque burden, neuronal degeneration, neuroinflammation, and improvement of behavioral deficits in aged APP/PS1 mice. The ameliorated cerebral amyloidosis was associated with an enhanced Aβ clearance of peripheral monocytes. In conclusion, our study provides evidence that immune system rejuvenation represents a promising therapeutic approach for AD.