Publication

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

Downloadable Content

Persistent URL
Last modified
  • 05/21/2025
Type of Material
Authors
    Yuzhong Zhang, The People's Hospital of LonghuaZhou Liu, Emory UniversityBing Ji, Emory UniversityShaoxiong Wu, Emory UniversityXiaowu Liu, Yiwei Medical Technology, Inc.Silun Wang, Yiwei Medical Technology, Inc.Liya Wang, Emory University
Language
  • English
Date
  • 2019-01-09
Publisher
  • Frontiers Media
Publication Version
Copyright Statement
  • © 2019 Zhang, Liu, Ji, Liu, Wu, Liu, Wang and Wang.
License
Final Published Version (URL)
Title of Journal or Parent Work
ISSN
  • 1663-4365
Volume
  • 10
Start Page
  • 424
End Page
  • 424
Grant/Funding Information
  • 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.
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.
Author Notes
Keywords
Research Categories
  • Biology, Neuroscience
  • Health Sciences, Radiology
  • Chemistry, Radiation

Tools

Relations

In Collection:

Items

Thumbnail Title File Description Date Uploaded Visibility Actions
file details Publication File - tn6fj.pdf Primary Content 2025-03-24 Public Download