Metabolomic analysis identifies alterations of amino acid metabolome signatures in the postmortem brain of Alzheimer’s disease

Yoon Hwan Kim, Hyun Soo Shim, Kyoung Heon Kim, Junghee Lee, Bong Chul Chung, Neil W. Kowall, Hoon Ryu, Jeongae Lee

Research output: Contribution to journalArticlepeer-review

23 Citations (Scopus)

Abstract

Despite significant advances in neuroscience research over the past several decades, the exact cause of AD has not yet fully understood. The metabolic hypothesis as well as the amyloid and tau hypotheses have been proposed to be associated with AD pathogenesis. In order to identify metabolome signatures from the postmortem brains of sporadic AD patients and control subjects, we performed ultra performance liquid chromatography coupled with linear ion trap-Orbitrap mass spectrometer (UPLC-LTQ–Orbitrap-MS). Not only our study identified new metabolome signatures but also verified previously known metabolome profiles in the brain. Statistical modeling of the analytical data and validation of the structural assignments discovered metabolic biomarkers associated with the AD pathogenesis. Interestingly, hypotaurin, myo-inositol and oxo-proline levels were markedly elevated in AD while glutamate and N-acetyl-aspartate were decreased in the postmortem brain tissue of AD patients. In addition, neurosteroid level such as cortisol was significantly increased in AD. Together, our data indicate that impaired amino acid metabolism is associated with AD pathogenesis and the altered amino acid signatures can be useful diagnostic biomarkers of AD. Thus, modulation of amino acid metabolism may be a possible therapeutic approach to treat AD.

Original languageEnglish
Pages (from-to)376-389
Number of pages14
JournalExperimental Neurobiology
Volume28
Issue number3
DOIs
Publication statusPublished - 2019 Jun 1

Bibliographical note

Funding Information:
This study was supported by a grant from the Korea Institute of Science and Technology (2N42780).This study was supported by NIH R01NS067283 (H.R.). This study was also supported bythe National Research Foundation of Korea Grant (NRF-2015M3A9A8030034 and NRF-2016M3C7A1904233) from the Ministry of Science, ICT and Future Planning, the National Research Council of Science & Technology (NST) Grant (No. CRC-15-04-KIST) from the Korean Government (MSIP), and Grants from Korea Institute of Science and Technology (2E29230, 2E29221, and 2E28030).

Publisher Copyright:
Copyright © Experimental Neurobiology 2019.

Keywords

  • Alzheimer’s disease
  • Amino acid metabolism
  • Biomarkers
  • Liquid chromatography mass spectrometry
  • Metabolomics

ASJC Scopus subject areas

  • Clinical Neurology
  • Cellular and Molecular Neuroscience

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