Journal
NEUROBIOLOGY OF AGING
Volume 36, Issue 1, Pages 68-80Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.neurobiolaging.2014.08.004
Keywords
Alzheimer's disease; Frontal cortex; Entorhinal cortex; Precuneus; Purine metabolism; Metabolomics; Mass spectrometry
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Funding
- Seventh Framework Program of the European Commission [278486]
- Institute Carlos III, FIS [PI1100968, PI1101532, PI1300584]
- Programa de Formacion de Personal Investigador no doctor del Departamento de Educacion, Politica Linguistica y Cultura of the Basque Government
- ICREA Funding Source: Custom
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The neuroprotective role of adenosine and the deregulation of adenosine receptors in Alzheimer's disease (AD) have been extensively studied in recent years. However, little is known about the involvement of purine metabolism in AD. We started by analyzing gene expression in the entorhinal cortex of human controls and AD cases with whole-transcript expression arrays. Once we identified deregulation of the cluster purine metabolism, messenger RNA expression levels of 23 purine metabolism genes were analyzed with qRT-PCR in the entorhinal cortex, frontal cortex area 8, and precuneus at stages I-II, III-IV, and V-VI of Braak and Braak and controls. APRT, DGUOK, POLR3B, ENTPD3, AK5, NME1, NME3, NME5, NME7, and ENTPD2 messenger RNAs were deregulated, with regional variations, in AD cases when compared with controls. In addition, liquid chromatography mass spectrometry based metabolomics in the entorhinal cortex identified altered levels of dGMP, glycine, xanthosine, inosine diphosphate, guanine, and deoxyguanosine, all implicated in this pathway. Our results indicate stage- and region-dependent deregulation of purine metabolism in AD. (C) 2015 Elsevier Inc. All rights reserved.
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