Klotho Improves Alzheimer's Disease-like Pathology and Cognitive Deficits in APP/PS1 Mice

Alzheimer's disease (AD) is the most common type of senile dementia. The anti‐aging gene Klotho is reported to decline in the brain of AD patients and animals. However, the role of Klotho in the progression of AD remains elusive. The present study explored the effects and underlying mechanism of Klotho in a mouse model of AD. The upregulation of cerebral Klotho expression was mediated by an intracerebroventricular injection of a lentiviral vector that encoded Klotho (LV‐KL) in 7‐month‐old APP/PS1 transgenic mice. Three months later, LV‐KL significantly induced Klotho overexpression in the brain and effectively ameliorated cognitive deficit and Alzheimer's disease‐like pathology in APP/PS1 mice. LV‐KL induced autophagy activation both in AD mice and BV2 murine microglia. These results suggest that the upregulation of Klotho expression in the brain may promote the autophagic clearance of Aβ and protect against cognitive deficits in AD mice. These findings highlight the preventive and therapeutic potential of Klotho for the treatment of AD. Support or Funding Information This work was supported by the National Science Foundation of China (81473219), and partly by targeting drug delivery system of Sichuan Province Youth Science and Technology Innovation Team (2016TD0001) and 111 Project of the National Ministry of Education (B18035). This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .