title: Proteome-wide characterization of signalling interactions in the hippocampal CA4/DG subfield of patients with Alzheimer's disease.
abstract: Alzheimer's disease (AD) is the most common form of dementia; however, mechanisms and biomarkers remain unclear. Here, we examined hippocampal CA4 and dentate gyrus subfields, which are less studied in the context of AD pathology, in post-mortem AD and control tissue to identify possible biomarkers. We performed mass spectrometry-based proteomic analysis combined with label-free quantification for identification of differentially expressed proteins. We identified 4,328 proteins, of which 113 showed more than 2-fold higher or lower expression in AD hippocampi than in control tissues. Five proteins were identified as putative AD biomarkers (MDH2, PCLO, TRRAP, YWHAZ, and MUC19 isoform 5) and were cross-validated by immunoblotting, selected reaction monitoring, and MALDI imaging. We also used a bioinformatics approach to examine upstream signalling interactions of the 113 regulated proteins. Five upstream signalling (IGF1, BDNF, ZAP70, MYC, and cyclosporin A) factors showed novel interactions in AD hippocampi. Taken together, these results demonstrate a novel platform that may provide new strategies for the early detection of AD and thus its diagnosis.
authors.affiliation: Center for Cognition and Sociality, Institute for Basic Science, Daejeon 305-811, Republic of Korea.|Mass Spectrometry Research Center, Korea Basic Science Institute, 804-1 Yangcheong-ri, Ochang-eup, Cheongwon-gun, Chungbuk 363-883, Republic of Korea.
authors.forename: Jae
authors.initials: J
authors.lastname: Ho Kim
authors.affiliation: Inserm U-1192, Laboratoire de Protéomique, Réponse Inflammatoire, Spectrométrie de Masse (PRISM), Université de Lille 1, Cité Scientifique, 59655 Villeneuve D'Ascq, France.
authors.forename: Julien
authors.initials: J
authors.lastname: Franck
authors.affiliation: Center for Cognition and Sociality, Institute for Basic Science, Daejeon 305-811, Republic of Korea.|Mass Spectrometry Research Center, Korea Basic Science Institute, 804-1 Yangcheong-ri, Ochang-eup, Cheongwon-gun, Chungbuk 363-883, Republic of Korea.|Graduate School of Analytical Science and Technology, Chungnam National University, Daejeon 305-764, Republic of Korea.
authors.forename: Taewook
authors.initials: T
authors.lastname: Kang
authors.affiliation: Department of Psychiatry, Morphological Brain Research Unit, University of Würzburg, Würzburg, Germany.
authors.forename: Helmut
authors.initials: H
authors.lastname: Heinsen
authors.affiliation: Brain Bank Consultants, Amsterdam, The Netherlands.
authors.forename: Rivka
authors.initials: R
authors.lastname: Ravid
authors.affiliation: Institut de Neuropatologia, Servei Anatomia Patologica, IDIBELL-Hospital Universitari de Bellvitge, Universitat de Barcelona, Spain.
authors.forename: Isidro
authors.initials: I
authors.lastname: Ferrer
authors.affiliation: Mass Spectrometry Research Center, Korea Basic Science Institute, 804-1 Yangcheong-ri, Ochang-eup, Cheongwon-gun, Chungbuk 363-883, Republic of Korea.|Graduate School of Analytical Science and Technology, Chungnam National University, Daejeon 305-764, Republic of Korea.
authors.forename: Mi
authors.initials: M
authors.lastname: Hee Cheon
authors.affiliation: Graduate School of Analytical Science and Technology, Chungnam National University, Daejeon 305-764, Republic of Korea.
authors.forename: Joo-Yong
authors.initials: JY
authors.lastname: Lee
authors.affiliation: Mass Spectrometry Research Center, Korea Basic Science Institute, 804-1 Yangcheong-ri, Ochang-eup, Cheongwon-gun, Chungbuk 363-883, Republic of Korea.|Graduate School of Analytical Science and Technology, Chungnam National University, Daejeon 305-764, Republic of Korea.
authors.forename: Jong
authors.initials: J
authors.lastname: Shin Yoo
authors.affiliation: School for Mental Health and Neuroscience, Department of Translational Neuroscience, Maastricht University, Maastricht, The Netherlands.
authors.forename: Harry W
authors.initials: HW
authors.lastname: Steinbusch
authors.affiliation: Inserm U-1192, Laboratoire de Protéomique, Réponse Inflammatoire, Spectrométrie de Masse (PRISM), Université de Lille 1, Cité Scientifique, 59655 Villeneuve D'Ascq, France.
authors.forename: Michel
authors.initials: M
authors.lastname: Salzet
authors.affiliation: Inserm U-1192, Laboratoire de Protéomique, Réponse Inflammatoire, Spectrométrie de Masse (PRISM), Université de Lille 1, Cité Scientifique, 59655 Villeneuve D'Ascq, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Fournier
authors.affiliation: Center for Cognition and Sociality, Institute for Basic Science, Daejeon 305-811, Republic of Korea.|Mass Spectrometry Research Center, Korea Basic Science Institute, 804-1 Yangcheong-ri, Ochang-eup, Cheongwon-gun, Chungbuk 363-883, Republic of Korea.|Graduate School of Analytical Science and Technology, Chungnam National University, Daejeon 305-764, Republic of Korea.
authors.forename: Young
authors.initials: Y
authors.lastname: Mok Park
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism*; D015415:Biomarkers / Q000378:metabolism; D018891:Dentate Gyrus / Q000378:metabolism*; D006801:Humans; D020543:Proteome; D015398:Signal Transduction
chemical_list: D015415:Biomarkers; D020543:Proteome