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Lentiviral vector–mediated overexpression of Klotho in the brain improves Alzheimer's disease–like pathology and cognitive deficits in mice

journal contribution
posted on 2019-06-01, 00:00 authored by Chen-Ye Zeng, Ting-Ting Yang, Hong-Jing Zhou, Yue Zhao, Xi Kuang, Wei DuanWei Duan, Jun-Rong Du
Alzheimer's disease (AD) is the most common type of senile dementia. The antiaging gene Klotho is reported to decline in the brain of patients and animals with AD. 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 amyloid precursor protein/presenilin 1 transgenic mice. Three months later, LV-KL significantly induced Klotho overexpression in the brain and effectively ameliorated cognitive deficit and AD-like pathology in amyloid precursor protein/presenilin 1 mice. LV-KL induced autophagy activation and protein kinase B/mammalian target of rapamycin inhibition 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 amyloid beta and protect against cognitive deficits in AD mice. These findings highlight the preventive and therapeutic potential of Klotho for the treatment of AD.

History

Journal

Neurobiology of aging

Volume

78

Pagination

18 - 28

Publisher

Elsevier

Location

Amsterdam, The Netherlands

eISSN

1558-1497

Language

eng

Publication classification

C1 Refereed article in a scholarly journal

Copyright notice

2019, Elsevier Inc.