Investigation of the human brain metabolome to identify potential markers for early diagnosis and therapeutic targets of Alzheimer's disease

Graham, Stewart F. and Chevallier, Olivier P. and Roberts, Dominic and Hölscher, Christian and Elliott, Christopher T. and Green, Brian D. (2013) Investigation of the human brain metabolome to identify potential markers for early diagnosis and therapeutic targets of Alzheimer's disease. Analytical Chemistry, 85 (3). pp. 1803-1811. ISSN 0003-2700

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Abstract

A study combining high resolution mass spectrometry (liquid chromatography-quadrupole time-of-flight-mass spectrometry, UPLC-QTof-MS) and chemometrics for the analysis of post-mortem brain tissue from subjects with Alzheimer's disease (AD) (n = 15) and healthy age-matched controls (n = 15) was undertaken. The huge potential of this metabolomics approach for distinguishing AD cases is underlined by the correct prediction of disease status in 94-97% of cases. Predictive power was confirmed in a blind test set of 60 samples, reaching 100% diagnostic accuracy. The approach also indicated compounds significantly altered in concentration following the onset of human AD. Using orthogonal partial least-squares discriminant analysis (OPLS-DA), a multivariate model was created for both modes of acquisition explaining the maximum amount of variation between sample groups (Positive Mode-R2 = 97%; Q2 = 93%; root mean squared error of validation (RMSEV) = 13%; Negative Mode-R2 = 99%; Q2 = 92%; RMSEV = 15%). In brain extracts, 1264 and 1457 ions of interest were detected for the different modes of acquisition (positive and negative, respectively). Incorporation of gender into the model increased predictive accuracy and decreased RMSEV values. High resolution UPLC-QTof-MS has not previously been employed to biochemically profile post-mortem brain tissue, and the novel methods described and validated herein prove its potential for making new discoveries related to the etiology, pathophysiology, and treatment of degenerative brain disorders.

Item Type:
Journal Article
Journal or Publication Title:
Analytical Chemistry
Uncontrolled Keywords:
/dk/atira/pure/subjectarea/asjc/1600/1602
Subjects:
?? analytical chemistry ??
ID Code:
69054
Deposited By:
Deposited On:
04 Apr 2014 13:00
Refereed?:
Yes
Published?:
Published
Last Modified:
15 Jul 2024 14:34