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Author Notes:

Correspondence: Liya Wang lwang30@emory.edu

These authors have contributed equally to this work: YZ and ZL.

LW contributed to project idea and supervision, manuscript revision, integrity of this manuscript.

YZ implemented the initial study and reviewed the manuscript.

ZL implemented the study, analyzed the data, and drafted the manuscript.

BJ analyzed the NMRS data.

LL and SWu collected the NMR data.

XL and SWa contributed to statistical analysis and reviewed the manuscript.

All authors had reviewed this manuscript critically and approved its final submission.

XL and SWa are employed by Yiwei Medical Technology, Inc.

The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Subjects:

Research Funding:

The authors gratefully acknowledge the financial support provided by the China Scholarship Council (CSC) to ZL for studying at Emory University, where he completed part of this project.

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Geriatrics & Gerontology
  • Neurosciences
  • Neurosciences & Neurology
  • nuclear magnetic resonance
  • Alzheimer's disease
  • metabolic change
  • neurochemistry
  • brain
  • MAGNETIC-RESONANCE-SPECTROSCOPY
  • MILD COGNITIVE IMPAIRMENT
  • HR-MAS SPECTROSCOPY
  • N-ACETYLASPARTATE
  • HIPPOCAMPAL METABOLITES
  • POSTERIOR CINGULATE
  • EX-VIVO
  • DEMENTIA
  • H-1
  • REDUCTION

Metabolite Profile of Alzheimer's Disease in the Frontal Cortex as Analyzed by HRMAS H-1 NMR

Tools:

Journal Title:

Frontiers in Aging Neuroscience

Volume:

Volume 10

Publisher:

, Pages 424-424

Type of Work:

Article | Final Publisher PDF

Abstract:

Background: Investigation on neurochemical changes in the frontal cortex in individuals with Alzheimer's disease (AD) and different Apolipoprotein E (APOE) genotypes, using ex vivo solid-state high-resolution NMR analysis, may lead to a better understanding of the neurochemistry associated with AD as well as new AD-specific metabolite biomarkers that might potentially improve the clinical diagnosis of AD. Methods: Intact tissue samples of the frontal cortex were obtained from 11 patients and 11 age-matched non-demented controls. Metabolite profiles in all samples were analyzed ex vivo, using solid-state high-resolution magic angle spinning (HRMAS) 600 MHz 1H nuclear magnetic resonance (NMR). A logistic regression analysis was used to rank metabolites based on their level of contribution in differentiating the AD patient tissues and the controls, and different AD-associated APOE genotypes (APOE ε4 vs. APOE ε3). Results: Tissue samples from the AD patients showed significantly lower NAA/Cr (p = 0.011), Ace/Cr (p = 0.027), GABA/Cr (p = 0.005), Asp/Cr (p < 0.0001), mI/Cr (p < 0.0001), and Tau/Cr (p = 0.021), and higher PCho/Cr (p < 0.0001), GPCho/Cr (p < 0.0001), and α&β-Glc/Cr (p < 0.0001) than the controls did. Specifically, a newly observed resonance at 3.71 ppm, referred to as α&β-Glc, was observed in 90.9% of the AD samples (10/11). Samples with APOE ε4 also exhibited higher PCho/Cr (p = 0.0002), GPCho/Cr (p = 0.0001), α&β-Glc/Cr (p < 0.0001), and lower Asp/Cr (p = 0.004) and GABA/Cr (p = 0.04) than the samples with APOE ε3 did. In the logistic regression analysis, PCho, GPCho, ASP, and α&β-Glc were found to be the most relevant metabolites for differentiating the AD patient tissues and the controls, and different APOE genotypes. Conclusion: HRMAS 1H NMR with high spectral resolution and sensitivity offers a powerful tool to gain quantitative information on AD associated neurochemical changes. There are important neurochemical differences in the frontal cortex between the AD patient tissues and the controls, and between those with different APOE genotypes. The resonance (α&β-Glc) found at 3.71 ppm in the AD patient tissues may be further investigated for its potential in the diagnosis and monitoring of AD.

Copyright information:

© 2019 Zhang, Liu, Ji, Liu, Wu, Liu, Wang and Wang.

This is an Open Access work distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/).
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