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Advanced Neurology

ORIGINAL RESEARCH ARTICLE
Emx1-Cre-mediated inactivation of PDK1

prevents plaque deposition in an Alzheimer’s
disease-like mouse model

3
3
2
Xiaolian Ye , Liyang Yao , Wenhao Chen , Wenkai Shao , Yimin Hu *,
1
2
2
1
Bing Zhang *, and Guiquan Chen *
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

Abstract

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
*Corresponding authors: in a 5×FAD mouse model, we employed a genetic approach to generate a mutant
Yimin Hu (guyueym@njmu.edu.cn) line, termed as Pdk1 cKO/5×FAD, in which PDK1 is inactivated, specifically in the
Bing Zhang
(zhangbing_nanjing@nju.edu.cn) developing cortex of 5×FAD mice through Emx1-Cre-mediated gene recombination.
Guiquan Chen We discovered that the Pdk1 cKO/5×FAD mice exhibited a massive reduction of plaque
(chenguiquan@nju.edu.cn) pathology compared with their 5×FAD littermates. We also demonstrated that gliosis
Citation: Ye X, Yao L, Chen W, was remarkably attenuated in Pdk1 cKO/5×FAD cortices and amyloid precursor
et al., 2022, Emx1-Cre-mediated protein levels were significantly lower in Pdk1 cKO/5×FAD cortices compared with
inactivation of PDK1 prevents
plaque deposition in an Alzheimer’s 5×FAD littermates. This study suggests that early inhibition on PDK1 may effectively
disease-like mouse model. Adv prevent AD-like neuropathology.
Neuro, 1(3): 153.
https://doi.org/10.36922/an.v1i3.153
Received: July 9, 2022 Keywords: Alzheimer’s disease; Plaque deposition; PDK1; Neuroinflammation; Amyloid
precursor protein; Conditional knockout
Accepted: October 17, 2022
Published Online: November 30, 2022
Copyright: © 2022 Author(s).
This is an Open Access article 1. Introduction
distributed under the terms of the
Creative Commons Attribution Alzheimer’s disease (AD) is the most common type of dementia in the elderly. The
License, permitting distribution, typical pathological hallmarks include extracellular amyloid β-protein (Aβ) deposition,
and reproduction in any medium, [1-3]
provided the original work is intracellular tangles formed by phosphorylated tau, and gliosis . The mechanisms
properly cited. underlying AD pathogenesis remain to be determined. A number of factors, including
[6]
Publisher’s Note: AccScience Aβ [4,5] and tau , have been identified as important factors for the etiology of AD. It is
Publishing remains neutral with believed that Aβ accumulation may induce inflammation and cause neuronal death in
regard to jurisdictional claims in [5]
published maps and institutional the brain . Many studies have demonstrated that Aβ is a major target for the treatment
affiliations. of AD [7-12] .

Volume 1 Issue 3 (2022) 1 https://doi.org/10.36922/an.v1i3.153