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J Proteome Res. 2016 May 6;15(5):1592-601. doi: 10.1021/acs.jproteome.6b00049. Epub 2016 Mar 28.

Novel Metabolite Biomarkers of Huntington's Disease As Detected by High-Resolution Mass Spectrometry.

Author information

1
Beaumont Health System, Beaumont Research Institute , 3811 West 13 Mile Road, Royal Oak, Michigan 48073, United States.
2
Institute of Brain Behavior and Mental Health, University of Manchester , Salford M6 8HD, United Kingdom.
3
Advanced Asset Technology Centre, Institute for Global Food Security, Queen's University Belfast , Belfast BT9 5BN, United Kingdom.

Abstract

Huntington's disease (HD) is a fatal autosomal-dominant neurodegenerative disorder that affects approximately 3-10 people per 100 000 in the Western world. The median age of onset is 40 years, with death typically following 15-20 years later. In this study, we biochemically profiled post-mortem frontal lobe and striatum from HD sufferers (n = 14) and compared their profiles with controls (n = 14). LC-LTQ-Orbitrap-MS detected a total of 5579 and 5880 features for frontal lobe and striatum, respectively. An ROC curve combining two spectral features from frontal lobe had an AUC value of 0.916 (0.794 to 1.000) and following statistical cross-validation had an 83% predictive accuracy for HD. Similarly, two striatum biomarkers gave an ROC AUC of 0.935 (0.806 to 1.000) and after statistical cross-validation predicted HD with 91.8% accuracy. A range of metabolite disturbances were evident including but-2-enoic acid and uric acid, which were altered in both frontal lobe and striatum. A total of seven biochemical pathways (three in frontal lobe and four in striatum) were significantly altered as a result of HD. This study highlights the utility of high-resolution metabolomics for the study of HD. Further characterization of the brain metabolome could lead to the identification of new biomarkers and novel treatment strategies for HD.

KEYWORDS:

Huntington’s disease; biomarkers; mass spectrometry; metabolomics

PMID:
27018767
DOI:
10.1021/acs.jproteome.6b00049
[Indexed for MEDLINE]

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