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Neurobiol Aging. 2015 Jan;36(1):68-80. doi: 10.1016/j.neurobiolaging.2014.08.004. Epub 2014 Aug 8.

Deregulation of purine metabolism in Alzheimer's disease.

Author information

1
Institute of Neuropathology, Bellvitge University Hospital-Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet de Llobregat, Spain.
2
Department of Experimental Medicine, University of Lleida-Biomedical Research Institute of Lleida, Lleida, Spain.
3
Neurometabolic Diseases Laboratory, IDIBELL, L'Hospitalet de Llobregat, Spain.
4
Neurometabolic Diseases Laboratory, IDIBELL, L'Hospitalet de Llobregat, Spain; Centre for Biomedical Research on Rare Diseases (CIBERER), Institute Carlos III, Madrid, Spain; Catalan Institution for Research and Advanced Studies (ICREA), Barcelona, Spain.
5
Institute of Neuropathology, Bellvitge University Hospital-Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet de Llobregat, Spain; University of Barcelona, Bellvitge Campus, L'Hospitalet de Llobregat, Spain; Centre for Networked Biomedical Research in Neurodegenerative Diseases (CIBERNED), Institute Carlos III, Madrid, Spain. Electronic address: 8082ifa@gmail.com.

Abstract

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.

KEYWORDS:

Alzheimer's disease; Entorhinal cortex; Frontal cortex; Mass spectrometry; Metabolomics; Precuneus; Purine metabolism

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