title: Deregulation of purine metabolism in Alzheimer's disease.
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.
authors.affiliation: Institute of Neuropathology, Bellvitge University Hospital-Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet de Llobregat, Spain.
authors.forename: Belén
authors.initials: B
authors.lastname: Ansoleaga
authors.affiliation: Department of Experimental Medicine, University of Lleida-Biomedical Research Institute of Lleida, Lleida, Spain.
authors.forename: Mariona
authors.initials: M
authors.lastname: Jové
authors.affiliation: Neurometabolic Diseases Laboratory, IDIBELL, L'Hospitalet de Llobregat, Spain.
authors.forename: Agatha
authors.initials: A
authors.lastname: Schlüter
authors.affiliation: Institute of Neuropathology, Bellvitge University Hospital-Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet de Llobregat, Spain.
authors.forename: Paula
authors.initials: P
authors.lastname: Garcia-Esparcia
authors.affiliation: Institute of Neuropathology, Bellvitge University Hospital-Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet de Llobregat, Spain.
authors.forename: Jesús
authors.initials: J
authors.lastname: Moreno
authors.affiliation: 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.
authors.forename: Aurora
authors.initials: A
authors.lastname: Pujol
authors.affiliation: Department of Experimental Medicine, University of Lleida-Biomedical Research Institute of Lleida, Lleida, Spain.
authors.forename: Reinald
authors.initials: R
authors.lastname: Pamplona
authors.affiliation: Department of Experimental Medicine, University of Lleida-Biomedical Research Institute of Lleida, Lleida, Spain.
authors.forename: Manuel
authors.initials: M
authors.lastname: Portero-Otín
authors.affiliation: 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.
authors.forename: Isidre
authors.initials: I
authors.lastname: Ferrer
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics / Q000378:metabolism; D000263:Adenylate Kinase / Q000235:genetics / Q000378:metabolism; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism*; D002853:Chromatography, Liquid; D003848:Deoxyguanine Nucleotides / Q000378:metabolism; D018728:Entorhinal Cortex / Q000378:metabolism*; D005260:Female; D015870:Gene Expression / Q000235:genetics*; D005786:Gene Expression Regulation / Q000235:genetics*; D005998:Glycine / Q000378:metabolism; D006801:Humans; D008297:Male; D013058:Mass Spectrometry; D008875:Middle Aged; D011687:Purines / Q000378:metabolism*; D012320:RNA Polymerase III / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012263:Ribonucleosides / Q000378:metabolism; D014970:Xanthines
chemical_list: D003848:Deoxyguanine Nucleotides; D011687:Purines; D012333:RNA, Messenger; D012263:Ribonucleosides; D014970:Xanthines; C007257:2'-deoxyguanosine 5'-phosphate; C005893:xanthosine; D000263:Adenylate Kinase; C118782:adenylate kinase 5; C468558:POLR3B protein, human; D012320:RNA Polymerase III; D000251:Adenosine Triphosphatases; C027201:ectoATPase; D005998:Glycine; C030985:purine
keywords: Alzheimer's disease; Entorhinal cortex; Frontal cortex; Mass spectrometry; Metabolomics; Precuneus; Purine metabolism