Metabolic signatures of human Alzheimer’s disease (AD): 1H NMR analysis of the polar metabolome of post-mortem brain tissue. Authors: Stewart F. Graham1*, Christian Holscher2 and Brian D. Green1. 1
Institute for Global Food Security, Queen’s University Belfast, Stranmillis Road, Belfast,
BT9 5AG, Northern Ireland,UK. . 2
Division of Biomedical and Life Sciences, Furness Building, Lancaster University,
Lancaster LA1 4YG, UK. * Corresponding Author Tel: +44 2890976562; Fax: +44 289097656; e-mail:
[email protected] Abbreviated Title: 1H NMR analysis of post-mortem human brain tissue. Acknowledgements: This work was supported by a pilot grant from Alzheimer’s Research, UK (ARUK)-ARUK-PPG2011B-8. The authors’ work is also supported by a Network Cooperation Grant-ARUK-NCG2012B-5. We gratefully acknowledge the Newcastle Brain Research Trust for the donation of human tissue used in this study.
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Abstract Brain tissue from so-called Alzheimer’s disease (AD) mouse models has previously been examined using 1H NMR-metabolomics, but comparable information concerning human AD is negligible. Since no animal model recapitulates all the features of human AD we undertook the first 1H NMR-metabolomics investigation of human AD brain tissue. Human postmortem tissue from 15 AD subjects and 15 age-matched controls was prepared for analysis through a series of lyophilised, milling, extraction and randomisation steps and samples were analysed using 1H NMR. Using partial least squares discriminant analysis, a model was built using data obtained from brain extracts. Analysis of brain extracts led to the elucidation of 24 metabolites. Significant elevations in brain alanine (15.4%) and taurine (18.9%) were observed in AD patients (p≤0.05). Pathway topology analysis implicated either dysregulation of Taurine and hypotaurine metabolism or Alanine, aspartate and glutamate metabolism. Furthermore, screening of metabolites for AD biomarkers demonstrated that individual metabolites weakly discriminated cases of AD (ROC AUC
