Autophagy enhancer carbamazepine alleviates memory deficits and cerebral amyloid-β pathology in a mouse model of Alzheimer's disease

Lixi Li, Sufang Zhang, Xin Zhang, Ting Li, Yu Tang, Hui Liu, Wendi Yang, Weidong Le

Research output: Contribution to journalArticle

84 Scopus citations

Abstract

Autophagy plays an important role in Alzheimer's disease (AD). It has been reported that autophagic flux is altered in patients with AD, and application of the autophagy enhancer rapamycin may alleviate the cognitive impairment and amyloid-β (Aβ) neuropathology in transgenic animal model of AD. Since rapamycin is also an immune suppressor, there is a concern that long-term use of rapamycin may bring severe unwanted side effects. The aim of this study is to test if carbamazepine (CBZ), an anti-epileptic drug that has a potent autophagy enhancement effect, has anti-AD effects in APPswe/PS1deltaE9 transgenic mice model of AD. We found that APPswe/PS1deltaE9 mice display increased autophagic activity accompanied by decreased mTOR activity. After three months treatment with CBZ in the APPswe/PS1deltaE9 mice, we demonstrated that the spatial learning and memory deficits in these mice are significantly alleviated. We also documented that the cerebral amyloid plaque burden and Aβ42 levels in these mice are significantly reduced. Furthermore, we showed that CBZ significantly enhances the autophagic flux in the APPswe/PS1deltaE9 mice which is unlikely via mTOR-dependent autophagy pathway. These data suggest that long-term CBZ treatment may have a protective effect in AD mouse model possibly through enhancing the autophagic flux.

Original languageEnglish (US)
Pages (from-to)433-441
Number of pages9
JournalCurrent Alzheimer Research
Volume10
Issue number4
DOIs
StatePublished - 2013

Keywords

  • Alzheimer's disease
  • Amyloid-β
  • Autophagy
  • Carbamazepine
  • mTOR pathway
  • Spatial memory

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

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