The Protective Effect of Vanadium on Cognitive Impairment and the Neuropathology of Alzheimer's Disease in APPSwe/PS1dE9 Mice.

Zhijun He,Xiaoqian Li,Huazhang Zhu,Qiong Liu,Jiazuan Ni,Nan Li,Qingguo Xie,Chaofan Hou,Xiubo Du,Xia Hu,Shuangxue Han,Chong Wu

doi:10.3389/fnmol.2020.00021

Abstract

Alzheimer’s disease (AD) is a widely distributed neurodegenerative disease characterized clinically by cognitive deficits and pathologically by formation of amyloid-β (Aβ) plaque and neurofibrillary tangles (NFTs) in the brain. Vanadium is a biological trace element that has a function to mimic insulin for diabetes. Bis(ethylmaltolato) oxidovanadium (IV) (BEOV) has been reported to have a hypoglycemic property, but its effect on AD remains unclear. In this study, BEOV was supplemented at doses of 0.2 and 1.0 mmol/L to the AD model mice APPSwe/PS1dE9 for 3 months. The results showed that BEOV substantially ameliorated glucose metabolic disorder as well as synaptic and behavioral deficits of the AD mice. Further investigation revealed that BEOV significantly reduced Aβ generation by increasing the expression of peroxisome proliferator-activated receptor gamma and insulin-degrading enzyme and by decreasing β-secretase 1 in the hippocampus and cortex of AD mice. BEOV also reduced tau hyperphosphorylation by inhibiting protein tyrosine phosphatase-1B and regulating the pathway of insulin receptor/insulin receptor substrate-1/protein kinase B/glycogen synthase kinase 3 beta. Furthermore, BEOV could enhance autophagolysosomal fusion and restore autophagic flux to increase the clearance of Aβ deposits and phosphorylated tau in the brains of AD mice. Collectively, the present study provides solid data for revealing the function and mechanism of BEOV on AD pathology.

Highlights

Alzheimer’s disease (AD), an age-related neurodegenerative disease first described by German neurologist Alois Alzheimer in 1907, is the most common type of dementia worldwide (Vinters, 2015)
No significant alterations were detected in body weight and the levels of serum AST, urea, and creatinine among the APPSwe/PS1dE9 AD mice and BEOV-treated AD mice (Supplementary Figure S1), which indicated no damage to liver and renal function by BEOV at the doses used in this article
To test whether BEOV treatment had any impact on memory impairment, we subjected 9-month-old WT mice, APPSwe/PS1dE9 AD mice, and BEOV-treated AD mice to the Morris water maze (MWM) test to evaluate their memory and spatial learning

Summary

Introduction

Alzheimer’s disease (AD), an age-related neurodegenerative disease first described by German neurologist Alois Alzheimer in 1907, is the most common type of dementia worldwide (Vinters, 2015). In 2015, AD-related cost was over 600 billion dollars worldwide and over 200 billion dollars in the US alone (Alzheimer’s Association, 2016). If this disease remains unchecked, the number. Type 2 diabetes mellitus (T2DM) increases the risk of developing AD (Akter et al, 2011; Vagelatos and Eslick, 2013) and AD patients exhibit disturbed energy metabolism and insulin resistant in the brain, possibly due to impairments of insulin signaling (Talbot et al, 2012; Chen and Zhong, 2013). Tau pathology is inferred to induce brain insulin resistance, which is instrumental for cognitive and metabolic impairments in AD patients. Based on the link between AD and T2DM, it is reasonable to think that insulin enhancement agents could have the capacity to prevent AD progression and drugs for T2DM treatment such as the peroxisome proliferator-activated receptor γ (PPARγ) agonists are potential candidates for the treatment of AD (Landreth et al, 2008; Nicolakakis and Hamel, 2010)

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Conclusion