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SUCLG2 identified as both a determinator of CSF Aβ1-42 levels and an attenuator of cognitive decline in Alzheimer's disease

Ramirez, Alfredo ; van der Flier, Wiesje M. ; Herold, Christine ; Ramonet, David ; Heilmann, Stefanie ; Lewczuk, Piotr ; Popp, Julius ; Lacour, André ; Drichel, Dmitriy ; Louwersheimer, Eva ; Kummer, Markus P. ; Cruchaga, Carlos ; Hoffmann, Per ; Teunissen, Charlotte ; Holstege, Henne ; Kornhuber, Johannes ; Peters, Oliver ; Naj, Adam C. ; Chouraki, Vincent ; Bellenguez, Céline ; Gerrish, Amy ; Heun, Reiner ; Frölich, Lutz ; Hüll, Michael ; Buscemi, Lara ; Herms, Stefan ; Kölsch, Heike ; Scheltens, Philip ; Breteler, Monique M. ; Rüther, Eckart ; Wiltfang, Jens ; Goate, Alison ; Jessen, Frank ; Maier, Wolfgang ; Heneka, Michael T. ; Becker, Tim ; Nöthen, Markus M.

In: Human Molecular Genetics, 2014, vol. 23, no. 24, p. 6644-6658

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    Titel
    • SUCLG2 identified as both a determinator of CSF Aβ1-42 levels and an attenuator of cognitive decline in Alzheimer's disease
    Autor
    • Ramirez, Alfredo. Department of Psychiatry and Psychotherapy
    • van der Flier, Wiesje M.. Department of Neurology and Alzheimer Center, Neuroscience Campus Amsterdam, VU University Medical Center, 1081 HZ, Amsterdam, The Netherlands
    • Herold, Christine. German Center for Neurodegenerative Diseases (DZNE), 53175, Bonn, Germany
    • Ramonet, David. Clinical Neuroscience Unit, Department of Neurology
    • Heilmann, Stefanie. Institute of Human Genetics
    • Lewczuk, Piotr. Department of Psychiatry and Psychotherapy, Universitätsklinikum Erlangen, and Friedrich-Alexander Universität Erlangen-Nürnberg, 91054, Erlangen, Germany
    • Popp, Julius. Department of Psychiatry and Psychotherapy
    • Lacour, André. German Center for Neurodegenerative Diseases (DZNE), 53175, Bonn, Germany
    • Drichel, Dmitriy. German Center for Neurodegenerative Diseases (DZNE), 53175, Bonn, Germany
    • Louwersheimer, Eva. Department of Neurology and Alzheimer Center, Neuroscience Campus Amsterdam, VU University Medical Center, 1081 HZ, Amsterdam, The Netherlands
    • Kummer, Markus P.. Clinical Neuroscience Unit, Department of Neurology
    • Cruchaga, Carlos. Department of Psychiatry
    • Hoffmann, Per. Institute of Human Genetics
    • Teunissen, Charlotte. Department of Neurology and Alzheimer Center, Neuroscience Campus Amsterdam, VU University Medical Center, 1081 HZ, Amsterdam, The Netherlands
    • Holstege, Henne. Department of Neurology and Alzheimer Center, Neuroscience Campus Amsterdam, VU University Medical Center, 1081 HZ, Amsterdam, The Netherlands
    • Kornhuber, Johannes. Department of Psychiatry and Psychotherapy, Universitätsklinikum Erlangen, and Friedrich-Alexander Universität Erlangen-Nürnberg, 91054, Erlangen, Germany
    • Peters, Oliver. Department of Psychiatry, Charité, 14050, Berlin, Germany
    • Naj, Adam C.. Center for Clinical Epidemiology & Biostatistics, University of Pennsylvania, PA 19104, Philadelphia, USA
    • Chouraki, Vincent. Department of Neurology, Boston University School of Medicine, MA 02118, Boston, USA
    • Bellenguez, Céline. Inserm, U744, Lille 59000, France
    • Gerrish, Amy. Institute of Psychological Medicine and Clinical Neurosciences, MRC Centre for Neuropsychiatric Genetics & Genomics, Cardiff University, Cardiff, UK
    • Heun, Reiner. Department of Psychiatry and Psychotherapy
    • Frölich, Lutz. Department of Geriatric Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, 68159, Mannheim, Germany
    • Hüll, Michael. Centre for Geriatric Medicine and Section of Gerontopsychiatry and Neuropsychology, Medical School, University of Freiburg, 79106, Freiburg, Germany
    • Buscemi, Lara. Department of Fundamental Neurosciences, UNIL, 1005 Lausanne, Switzerland and
    • Herms, Stefan. Institute of Human Genetics
    • Kölsch, Heike. Department of Psychiatry and Psychotherapy
    • Scheltens, Philip. Department of Neurology and Alzheimer Center, Neuroscience Campus Amsterdam, VU University Medical Center, 1081 HZ, Amsterdam, The Netherlands
    • Breteler, Monique M.. German Center for Neurodegenerative Diseases (DZNE), 53175, Bonn, Germany
    • Rüther, Eckart. Department of Psychiatry and Psychotherapy, University of Göttingen, 37075 Göttingen, Germany
    • Wiltfang, Jens. Department of Psychiatry and Psychotherapy, University of Göttingen, 37075 Göttingen, Germany
    • Goate, Alison. Department of Psychiatry
    • Jessen, Frank. Department of Psychiatry and Psychotherapy
    • Maier, Wolfgang. Department of Psychiatry and Psychotherapy
    • Heneka, Michael T.. Clinical Neuroscience Unit, Department of Neurology
    • Becker, Tim. Institute for Medical Biometry, Informatics, and Epidemiology, University of Bonn, 53127, Bonn, Germany
    • Nöthen, Markus M.. Institute of Human Genetics
    Dokumententyp
    • Postprint
    Sprache
    • Englisch
    Veröffentlicht in
    • Human Molecular Genetics, 2014, vol. 23, no. 24, p. 6644-6658. Oxford University Press
    Andere elektronische Ausgabe
    Klassifikation
    • Gesundheit
    OAI-PMH-ID
    • oai:doc.rero.ch:296237
    Summary
    Cerebrospinal fluid amyloid-beta 1-42 (Aβ1-42) and phosphorylated Tau at position 181 (pTau181) are biomarkers of Alzheimer's disease (AD). We performed an analysis and meta-analysis of genome-wide association study data on Aβ1-42 and pTau181 in AD dementia patients followed by independent replication. An association was found between Aβ1-42 level and a single-nucleotide polymorphism in SUCLG2 (rs62256378) (P = 2.5×10−12). An interaction between APOE genotype and rs62256378 was detected (P = 9.5 × 10−5), with the strongest effect being observed in APOE-ε4 noncarriers. Clinically, rs62256378 was associated with rate of cognitive decline in AD dementia patients (P = 3.1 × 10−3). Functional microglia experiments showed that SUCLG2 was involved in clearance of Aβ1-42