Study on Urine Metabolic Profile of Aβ25–35-Induced Alzheimer's Disease Using UHPLC-Q-TOF-MS

Liu, Yuanyuan; Wei, Mengying; Yue, Kexin; Hu, Mingxin; Li, Shizhe; Men, Lihui; Pi, Zifeng; Liu, Zhiqiang

doi:10.1016/j.neuroscience.2018.10.001

Cited by 31 publications

(18 citation statements)

References 67 publications

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“…It has been reported that amyloid plaques formed by atypical cleavage of amyloid precursor protein play a leading role in the pathogenesis of AD [2]. Previous reports have underscored that the AD model obtained by injecting Aβ25–35 into the rat brain is stable, reliable, and comparable to human dementia [3]. Therefore, in the current study, Aβ25–35‐injected rats were used as a model to study the change in metabolite profile during AD.…”

Section: Introductionmentioning

confidence: 97%

A metabolomic study of the urine of rats with Alzheimer's disease and the efficacy of Ding‐Zhi‐Xiao‐Wan on the afflicted rats

Wang

Liu

et al. 2020

J of Separation Science

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As a well-known traditional Chinese medicine formula, Ding-Zhi-Xiao-Wan has long been used for the routine treatment of Alzheimer's disease. However, the mechanism of Ding-Zhi-Xiao-Wan in treating Alzheimer's disease is unclear. Therefore, a nontargeted metabolomics method based on ultrahigh performance liquid chromatography with quadrupole time-of-flight mass spectrometry has been established to explore the metabolic variations in the urine of Alzheimer's disease rats and investigate the therapeutic mechanism of Ding-Zhi-Xiao-Wan on Alzheimer's disease. To develop a better rat model of Alzheimer's disease, amyloid β25-35 was injected into the bilateral hippocampus of Sprague-Dawley rats. Multivariate analysis approaches were applied to differentiate the urine components between the four groups. Thereafter, a targeted metabolomics method was used to verify the identified endogenous metabolites and determine the mechanism of action of Ding-Zhi-Xiao-Wan. Altogether, 26 potential biomarkers were found, of which 15 biomarkers (10 of which are potential biomarkers found in nontargeted metabolomics) were identified. The results show that Ding-Zhi-Xiao-Wan mainly affects the pathways of taurine and hypotaurine metabolism, tryptophan metabolism, and phenylalanine metabolism. Ding-Zhi-Xiao-Wan might play a role in the treatment of Alzheimer's disease by mediating antioxidative stress, regulation of energy metabolism, improvement of intestinal microbes, and protection of nerve cells.

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Section: Introductionmentioning

confidence: 97%

A metabolomic study of the urine of rats with Alzheimer's disease and the efficacy of Ding‐Zhi‐Xiao‐Wan on the afflicted rats

Wang

Liu

et al. 2020

J of Separation Science

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“…Metabolomics involves the comprehensive analysis of small-molecule metabolites in a given biological matrix and their response to disease, drugs, diet, and lifestyle [3,10]. Our group and others have demonstrated the potential of metabolomics to successfully differentiate neurodegenerative diseases from healthy controls, while revealing insights into the underlying biochemistry [3,[11][12][13][14][15][16][17][18][19][20][21][22]. However, these studies have not shown to have any clinical utility.…”

Section: Introductionmentioning

confidence: 99%

Targeted Metabolic Profiling of Urine Highlights a Potential Biomarker Panel for the Diagnosis of Alzheimer’s Disease and Mild Cognitive Impairment: A Pilot Study

et al. 2020

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The lack of sensitive and specific biomarkers for the early detection of mild cognitive impairment (MCI) and Alzheimer’s disease (AD) is a major hurdle to improving patient management. A targeted, quantitative metabolomics approach using both 1H NMR and mass spectrometry was employed to investigate the performance of urine metabolites as potential biomarkers for MCI and AD. Correlation-based feature selection (CFS) and least absolute shrinkage and selection operator (LASSO) methods were used to develop biomarker panels tested using support vector machine (SVM) and logistic regression models for diagnosis of each disease state. Metabolic changes were investigated to identify which biochemical pathways were perturbed as a direct result of MCI and AD in urine. Using SVM, we developed a model with 94% sensitivity, 78% specificity, and 78% AUC to distinguish healthy controls from AD sufferers. Using logistic regression, we developed a model with 85% sensitivity, 86% specificity, and an AUC of 82% for AD diagnosis as compared to cognitively healthy controls. Further, we identified 11 urinary metabolites that were significantly altered to include glucose, guanidinoacetate, urocanate, hippuric acid, cytosine, 2- and 3-hydroxyisovalerate, 2-ketoisovalerate, tryptophan, trimethylamine N oxide, and malonate in AD patients, which are also capable of diagnosing MCI, with a sensitivity value of 76%, specificity of 75%, and accuracy of 81% as compared to healthy controls. This pilot study suggests that urine metabolomics may be useful for developing a test capable of diagnosing and distinguishing MCI and AD from cognitively healthy controls.

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“…As a result, microglia are often used as cellular models to study neuroinflammation. And Aβ25‐35–induced neuronal cells were wildly used to construct AD cell models (Li et al, 2017; Liu et al, 2018). Thus, novel approaches that could ameliorate neurotoxicity and neuroinflammation are needed to improve AD treatment.…”

Section: Introductionmentioning

confidence: 99%

Retracted: MiR‐485‐3p serves as a biomarker and therapeutic target of Alzheimer's disease via regulating neuronal cell viability and neuroinflammation by targeting AKT3

Liu

et al. 2020

Molec Gen & Gen Med

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Study on Urine Metabolic Profile of Aβ25–35-Induced Alzheimer's Disease Using UHPLC-Q-TOF-MS

Cited by 31 publications

References 67 publications

A metabolomic study of the urine of rats with Alzheimer's disease and the efficacy of Ding‐Zhi‐Xiao‐Wan on the afflicted rats

A metabolomic study of the urine of rats with Alzheimer's disease and the efficacy of Ding‐Zhi‐Xiao‐Wan on the afflicted rats

Targeted Metabolic Profiling of Urine Highlights a Potential Biomarker Panel for the Diagnosis of Alzheimer’s Disease and Mild Cognitive Impairment: A Pilot Study

Retracted: MiR‐485‐3p serves as a biomarker and therapeutic target of Alzheimer's disease via regulating neuronal cell viability and neuroinflammation by targeting AKT3

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