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Comparative Metabolomics Analysis Reveals Key Metabolic Mechanisms and Protein Biomarkers in Alzheimer’s Disease

Authors
  • Dai, Zhao1, 2
  • Hu, Tian1
  • Su, Shijie1
  • Liu, Jinman1
  • Ma, Yinzhong3
  • Zhuo, Yue3
  • Fang, Shuhuan1
  • Wang, Qi1
  • Mo, Zhizhun4
  • Pan, Huafeng1
  • Fang, Jiansong1
  • 1 Guangzhou University of Chinese Medicine, Guangzhou , (China)
  • 2 First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou , (China)
  • 3 Chinese Academy of Sciences, Shenzhen , (China)
  • 4 Shenzhen Traditional Chinese Medicine Hospital, Shenzhen , (China)
Type
Published Article
Journal
Frontiers in Pharmacology
Publisher
Frontiers Media SA
Publication Date
May 25, 2022
Volume
13
Identifiers
DOI: 10.3389/fphar.2022.904857
Source
Frontiers
Keywords
Disciplines
  • Pharmacology
  • Original Research
License
Green

Abstract

Alzheimer’s disease (AD) is one of the most common progressive neurodegenerative diseases, accompanied by global alterations in metabolic profiles. In the past 10 years, over hundreds of metabolomics studies have been conducted to unravel metabolic changes in AD, which provides insight into the identification of potential biomarkers for diagnosis, treatment, and prognostic assessment. However, since different species may lead to systemic abnormalities in metabolomic profiles, it is urgently needed to perform a comparative metabolomics analysis between AD animal models and human patients. In this study, we integrated 78 metabolic profiles from public literatures, including 11 metabolomics studies in different AD mouse models and 67 metabolomics studies from AD patients. Metabolites and enrichment analysis were further conducted to reveal key metabolic pathways and metabolites in AD. We totally identified 14 key metabolites and 16 pathways that are both differentially significant in AD mouse models and patients. Moreover, we built a metabolite-target network to predict potential protein markers in AD. Finally, we validated HER2 and NDF2 as key protein markers in APP/PS1 mice. Overall, this study provides a comprehensive strategy for AD metabolomics research, contributing to understanding the pathological mechanism of AD.

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