Metabolomic Analysis Identifies Alterations of Amino Acid Metabolome Signatures in the Postmortem Brain of Alzheimer's Disease
Experimental Neurobiology
;
: 376-389, 2019.
Artigo
em Inglês
| WPRIM
| ID: wpr-763767
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 lutamate 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.
Texto completo:
DisponíveL
Índice:
WPRIM (Pacífico Ocidental)
Assunto principal:
Encéfalo
/
Neurociências
/
Hidrocortisona
/
Biomarcadores
/
Modelos Estatísticos
/
Cromatografia Líquida
/
Metaboloma
/
Metabolômica
/
Doença de Alzheimer
/
Amiloide
Tipo de estudo:
Fatores de risco
Limite:
Humanos
Idioma:
Inglês
Revista:
Experimental Neurobiology
Ano de publicação:
2019
Tipo de documento:
Artigo
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