Title:Autophagy Enhancer Carbamazepine Alleviates Memory Deficits and Cerebral Amyloid-β Pathology in a Mouse Model of Alzheimer's Disease
VOLUME: 10 ISSUE: 4
Author(s):Lixi Li, Sufang Zhang, Xin Zhang, Ting Li, Yu Tang, Hui Liu, Wendi Yang and Weidong Le
Affiliation:Institute of Neurology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, PR China.
Keywords:Amyloid-β, Alzheimer's disease, autophagy, carbamazepine, mTOR pathway, spatial memory
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.
