Metabolic signatures of human Alzheimer’s disease (AD): 1H NMR analysis of the polar metabolome of post-mortem brain tissue

• Published in: Metabolomics Vol. 10; no. 4; pp. 744 - 753
• Main Authors: Graham, Stewart F., Holscher, Christian, Green, Brian D.
• Format: Journal Article
• Language: English; Japanese
• Published: New York Springer US 01.08.2014
• Subjects: Biochemistry; Biomedical and Life Sciences; Biomedicine; Cell Biology; Developmental Biology; Life Sciences; Molecular Medicine; Original Article; Human; Clinical; Brain; Metabolomics; NMR; Alzheimer’s disease
• ISSN: 1573-3882; 1573-3890
• DOI: 10.1007/s11306-013-0610-1

Brain tissue from so-called Alzheimer’s disease (AD) mouse models has previously been examined using 1 H 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 1 H NMR-metabolomics investigation of human AD brain tissue. Human post-mortem 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 1 H 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 [receiver operating characteristic (ROC) AUC <0.67; p  < 0.05]. However, paired metabolites ratios (e.g. alanine/carnitine) were more powerful discriminating tools (ROC AUC = 0.76; p  < 0.01). This study further demonstrates the potential of metabolomics for elucidating the underlying biochemistry and to help identify AD in patients attending the memory clinic.