AccScience Publishing / AN / Volume 1 / Issue 3 / DOI: 10.36922/an.v1i3.153

Emx1-Cre-mediated inactivation of PDK1 prevents plaque deposition in an Alzheimer’s disease-like mouse model

Xiaolian Ye1 Liyang Yao2 Wenhao Chen3 Wenkai Shao2 Yimin Hu3* Bing Zhang1* Guiquan Chen2*
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1 Department of Radiology, Medical Imaging Center, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Institute of Medical Imaging and Artificial Intelligence, Jiangsu Key Laboratory of Molecular Medicine, Institute of Brain Science, Nanjing University, Nanjing, Jiangsu Province, 210008, China
2 Model Animal Research Center, Department of Neurology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Jiangsu Key Laboratory of Molecular Medicine, Nanjing University, 12 Xuefu Avenue, Nanjing, Jiangsu Province, 210061, China
3 Department of Anesthesiology, The Second Affiliated Changzhou People’s Hospital of Nanjing Medical University, Changzhou, Jiangsu, 213000, China
Advanced Neurology 2022, 1(3), 153
Submitted: 9 July 2022 | Accepted: 17 October 2022 | Published: 30 November 2022
© 2022 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( )

BX912, an inhibitor for 3-phosphoinositide-dependent protein kinase 1 (PDK1), has been shown to produce beneficial effects in mouse models of Alzheimer’s disease (AD). To test the hypothesis that early inhibition on PDK1 may prevent neuropathology in a 5×FAD mouse model, we employed a genetic approach to generate a mutant line, termed as Pdk1 cKO/5×FAD, in which PDK1 is inactivated, specifically in the developing cortex of 5×FAD mice through Emx1-Cre-mediated gene recombination. We discovered that the Pdk1 cKO/5×FAD mice exhibited a massive reduction of plaque pathology compared with their 5×FAD littermates. We also demonstrated that gliosis was remarkably attenuated in Pdk1 cKO/5×FAD cortices and amyloid precursor protein levels were significantly lower in Pdk1 cKO/5×FAD cortices compared with 5×FAD littermates. This study suggests that early inhibition on PDK1 may effectively prevent AD-like neuropathology.

Alzheimer’s disease
Plaque deposition
Amyloid precursor protein
Conditional knockout
National Natural Science Foundation of China
Natural Key Research and Development Program of China
Natural Science Foundation of Jiangsu
Changzhou Municipal Key Research Program

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Conflict of interest
The authors have no conflicts of interest to declare.
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Advanced Neurology, Electronic ISSN: 2810-9619 Published by AccScience Publishing