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Metabolomic signatures in peripheral blood associated with Alzheimer's disease amyloid-β-induced neuroinflammation

 Eosu Kim  ;  Young Sang Jung  ;  Hyunjeong Kim  ;  Jin Sup Kim  ;  Minsun Park  ;  Jihyeon Jeong  ;  Su Kyoung Lee  ;  Ho Geun Yoon  ;  Geum Sook Hwang  ;  Kee Namkoong 
 JOURNAL OF ALZHEIMERS DISEASE, Vol.42(2) : 421-433, 2014 
Journal Title
Issue Date
Alzheimer Disease/chemically induced* ; Alzheimer Disease/complications* ; Amyloid beta-Peptides/toxicity ; Animals ; Biomarkers/metabolism ; Disease Models, Animal ; Encephalitis/blood* ; Encephalitis/drug therapy ; Encephalitis/etiology* ; Encephalitis/pathology ; Gallic Acid/therapeutic use ; HEK293 Cells ; Hippocampus/drug effects ; Hippocampus/metabolism ; Humans ; Magnetic Resonance Spectroscopy ; Mice ; Mice, Inbred ICR ; Multivariate Analysis ; Peptide Fragments/toxicity ; Principal Component Analysis ; Pyruvic Acid/blood ; Transfection ; Tritium ; Tumor Necrosis Factor-alpha/metabolism*
Alzheimer's disease ; NMR ; biomarker ; creatine ; metabolomics ; neuroinflammation ; plasma ; pyruvate
Discovery of biomarkers in peripheral blood is a crucial step toward the early diagnosis and repetitive monitoring of treatment response for Alzheimer's disease (AD). Metabolomics is a promising technology that can identify unbiased biomarkers. To explore potential blood biomarkers for AD via metabolic profiling with high-resolution magic angle spinning nuclear magnetic resonance techniques, we identified changes in peripheral blood metabolomic profiles in response to amyloid-β (Aβ)-induced neuroinflammation and co-treatment with gallate, a phytochemical known to have anti-neuroinflammatory properties. Alzheimer's-like (AL) model mice were produced by intracerebroventricular infusion of Aβ and compared with normal control mice with infusion of vehicle. AL mice were treated with either gallate (treated AL mice) or vehicle (untreated AL mice). Metabolomic analyses of both whole blood and plasma showed a clear separation between untreated AL mice and the other two groups, with levels of several metabolites involved in energy metabolism, including pyruvate and creatine, being significantly reduced in untreated AL mice compared with control and treated AL mice. Gallate treatment suppressed Aβ-induced overproduction of the inflammatory cytokine tumor necrosis factor-α in the hippocampus and normalized plasma levels of the affected metabolites. These results suggest that plasma levels of several metabolites could be indicative of both brain pathology and therapeutic responses, supporting the possibility of a close relationship between central neuroinflammation and systemic metabolic disturbance. These findings also suggest the potential of NMR-based metabolomics as a method to identify novel plasma biomarkers for AD, which could be confirmed by future translational research with human patients.
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1. College of Medicine (의과대학) > Research Institute (부설연구소) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Biochemistry and Molecular Biology (생화학-분자생물학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Psychiatry (정신과학교실) > 1. Journal Papers
Yonsei Authors
Kim, Eosu(김어수) ORCID logo https://orcid.org/0000-0001-9472-9465
Namkoong, Kee(남궁기) ORCID logo https://orcid.org/0000-0003-1400-8057
Park, Min Sun(박민선)
Yoon, Ho Geun(윤호근) ORCID logo https://orcid.org/0000-0003-2718-3372
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