The Role of Variation at AβPP, PSEN1, PSEN2, and MAPT in Late Onset Alzheimer's Disease

Article type: Research Article

Authors: Gerrish, Amy¹ | Russo, Giancarlo¹ | Richards, Alexander¹ | Moskvina, Valentina¹ | Ivanov, Dobril¹ | Harold, Denise¹ | Sims, Rebecca¹ | Abraham, Richard¹ | Hollingworth, Paul¹ | Chapman, Jade¹ | Hamshere, Marian¹ | Pahwa, Jaspreet Singh¹ | Dowzell, Kimberley¹ | Williams, Amy¹ | Jones, Nicola¹ | Thomas, Charlene¹ | Stretton, Alexandra¹ | Morgan, Angharad R.¹ | Lovestone, Simon² | Powell, John³ | Proitsi, Petroula³ | Lupton, Michelle K.³ | Brayne, Carol⁴ | Rubinsztein, David C.⁵ | Gill, Michael⁶ | Lawlor, Brian⁶ | Lynch, Aoibhinn⁶ | Morgan, Kevin⁷ | Brown, Kristelle S.⁷ | Passmore, Peter A.⁸ | Craig, David⁸ | McGuinness, Bernadette⁸ | Todd, Stephen⁸ | Johnston, Janet A.⁸ | Holmes, Clive⁹ | Mann, David¹⁰ | Smith, A. David¹¹ | Love, Seth¹² | Kehoe, Patrick G.¹² | Hardy, John¹³ | Mead, Simon¹⁴ | Fox, Nick¹⁵ | Rossor, Martin¹⁵ | Collinge, John¹⁴ | Maier, Wolfgang¹⁶ | Jessen, Frank¹⁶ | Kölsch, Heike¹⁶ | Heun, Reinhard^{16; 17} | Schürmann, Britta¹⁶ | Bussche, Hendrik van den¹⁸ | Heuser, Isabella¹⁹ | Kornhuber, Johannes²⁰ | Wiltfang, Jens²¹ | Dichgans, Martin^{22; 23} | Frölich, Lutz²⁴ | Hampel, Harald²⁵ | Hüll, Michael²⁶ | Rujescu, Dan²⁶ | Goate, Alison M.²⁷ | Kauwe, John S. K²⁸ | Cruchaga, Carlos²⁷ | Nowotny, Petra²⁷ | Morris, John C.²⁷ | Mayo, Kevin²⁷ | Livingston, Gill²⁹ | Bass, Nicholas J.²⁹ | Gurling, Hugh²⁹ | McQuillin, Andrew²⁹ | Gwilliam, Rhian³⁰ | Deloukas, Panagiotis³⁰ | Davies, Gail^{31; 32} | Harris, Sarah E.^{31; 33} | Starr, John M.^{31; 34} | Deary, Ian J.^{31; 32} | Al-Chalabi, Ammar³⁵ | Shaw, Christopher E.³⁵ | Tsolaki, Magda³⁶ | Singleton, Andrew B.³⁷ | Guerreiro, Rita³⁷ | Mühleisen, Thomas W.^{38; 39} | Nöthen, Markus M.^{38; 39} | Moebus, Susanne⁴⁰ | Jöckel, Karl-Heinz⁴⁰ | Klopp, Norman⁴¹ | Wichmann, H-Erich^{41; 42; 43} | Carrasquillo, Minerva M⁴⁴ | Pankratz, V Shane⁴⁵ | Younkin, Steven G.⁴⁴ | Jones, Lesley¹ | Holmans, Peter A¹ | O'Donovan, Michael C.¹ | Owen, Michael J.¹ | Williams, Julie^{1; *}

Affiliations: [1] MRC Centre for Neuropsychiatric Genetics and Genomics, Department of Psychological Medicine and Neurology, School of Medicine, Neuroscience and Mental Health Research Institute, Cardiff University, Cardiff, UK | [2] King's College London, Institute of Psychiatry, Kings College, London, UK | [3] Department of Neuroscience, Institute of Psychiatry, Kings College, London, UK | [4] Institute of Public Health, University of Cambridge, Cambridge, UK | [5] Cambridge Institute for Medical Research, University of Cambridge, Cambridge, UK | [6] Mercer's Institute for Research on Aging, St. James Hospital and Trinity College, Dublin, Ireland | [7] Human Genetics Group, School of Molecular Medical Sciences, Queen's Medical Centre, University of Nottingham, UK | [8] Ageing Group, Centre for Public Health, School of Medicine, Dentistry and Biomedical Sciences, Queen's University Belfast, UK | [9] Division of Clinical Neurosciences, School of Medicine, University of Southampton, Southampton, UK | [10] Neurodegeneration and Mental Health Research Group, School of Community Based Medicine, University of Manchester, Salford, UK | [11] Oxford Project to Investigate Memory and Ageing, University of Oxford, John Radcliffe Hospital, Oxford, UK | [12] Dementia Research Group, University of Bristol Institute of Clinical Neurosciences, Frenchay Hospital, Bristol, UK | [13] Department of Molecular Neuroscience and Reta Lilla Weston Laboratories, Institute of Neurology, London, UK | [14] MRC Prion Unit and Department of Neurodegenerative Disease, Institute of Neurology, University College London | [15] Dementia Research Centre, Department of Neurodegenerative Diseases, UCL Institute of Neurology, London, UK | [16] Department of Psychiatry, University of Bonn, Bonn, Germany | [17] Radbourne Unit, Royal Derby Hospital, Derby, UK | [18] Institute of Primary Medical Care, University Medical Center Hamburg-Eppendorf, Germany | [19] Department of Psychiatry, Charit'e Berlin, Berlin, Germany | [20] Department of Psychiatry and Psychotherapy, University of Erlangen-Nuremberg, Germany | [21] LVR-Hospital Essen, Department of Psychiatry and Psychotherapy, University Duisburg-Essen, Germany | [22] Institute for Stroke and Dementia Research, Klinikum der Universität München, Munich, Germany | [23] Department of Neurology, Klinikum der Universität München, Munich, Germany | [24] Department of Geriatric Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany | [25] Department of Psychiatry, Psychosomatic Medicine and Psychotherapy, Goethe University, Frankfurt, Germany | [26] Ludwig-Maximilians-University, Department of Psychiatry, Munich, Germany | [27] Departments of Psychiatry, Neurology and Genetics, Washington University School of Medicine, St. Louis, Missouri, USA | [28] Department of Biology, Brigham Young University, Provo, Utah, USA | [29] Mental Health Unit, UCL, London, UK | [30] The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, UK | [31] Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK | [32] Department of Psychology, University of Edinburgh, Edinburgh, UK | [33] Medical Genetics, Molecular Medicine Centre, University of Edinburgh, Edinburgh, UK | [34] Alzheimer Scotland Dementia Research Centre, University of Edinburgh, Edinburgh, UK | [35] MRC Centre for Neurodegeneration Research, King's College London, Institute of Psychiatry, Department of Clinical Neuroscience, London, UK | [36] Third Department of Neurology, Aristotle University of Thessaloniki, Thessaloniki, Greece | [37] Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, Maryland, USA | [38] Department of Genomics, Life and Brain Center, University of Bonn, Bonn, Germany | [39] Institute of Human Genetics, University of Bonn, Bonn, Germany | [40] Institute for Medical Informatics, Biometry and Epidemiology, University Hospital of Essen, University Duisburg-Essen, Essen, Germany | [41] Institute of Epidemiology, Helmholtz Zentrum M¨nchen, German Research Center for Environmental Health, Neuherberg, Germany | [42] Institute of Medical Informatics, Biometry and Epidemiology, Ludwig-Maximilians-Universität, Munich, Germany | [43] Klinikum Grosshadern, Munich, Germany | [44] Department of Neuroscience, Mayo Clinic College of Medicine, Jacksonville, Florida, USA | [45] Division of Biomedical Statistics and Informatics, Mayo Clinic and Mayo Foundation, Rochester, Minnesota, USA

Correspondence: [*] Correspondence to: Julie Williams, MRC Centre for Neuropsychiatric Genetics and Genomics, Department of Psychological Medicine and Neurology, Henry Wellcome Building, Heath Park, Cardiff, CF14 4XN, UK. Tel.: +44 (0)2920 687067; Fax: +44 (0)2920 687068; E-mail: WilliamsJ@cardiff.ac.uk.

Keywords: Alzheimer's disease, amyloid-β protein precursor, genetics, human, MAPT protein, PSEN1 protein, PSEN2 protein

DOI: 10.3233/JAD-2011-110824

Journal: Journal of Alzheimer's Disease, vol. 28, no. 2, pp. 377-387, 2012