Alzheimer’s disease; Amyloid-beta; Cerebrospinal fluid; GWAS; Tau; Amyloid beta-Peptides; Apolipoproteins E; Biomarkers; Cell Cycle Proteins; GMNC protein, human; Peptide Fragments; tau Proteins; Amyloid beta-Peptides/cerebrospinal fluid; Apolipoproteins E/genetics; Biomarkers/cerebrospinal fluid; Humans; Peptide Fragments/cerebrospinal fluid; tau Proteins/cerebrospinal fluid; tau Proteins/genetics; Alzheimer Disease/pathology; Pathology and Forensic Medicine; Neurology (clinical); Cellular and Molecular Neuroscience
Abstract :
[en] Amyloid-beta 42 (Aβ42) and phosphorylated tau (pTau) levels in cerebrospinal fluid (CSF) reflect core features of the pathogenesis of Alzheimer's disease (AD) more directly than clinical diagnosis. Initiated by the European Alzheimer & Dementia Biobank (EADB), the largest collaborative effort on genetics underlying CSF biomarkers was established, including 31 cohorts with a total of 13,116 individuals (discovery n = 8074; replication n = 5042 individuals). Besides the APOE locus, novel associations with two other well-established AD risk loci were observed; CR1 was shown a locus for Aβ42 and BIN1 for pTau. GMNC and C16orf95 were further identified as loci for pTau, of which the latter is novel. Clustering methods exploring the influence of all known AD risk loci on the CSF protein levels, revealed 4 biological categories suggesting multiple Aβ42 and pTau related biological pathways involved in the etiology of AD. In functional follow-up analyses, GMNC and C16orf95 both associated with lateral ventricular volume, implying an overlap in genetic etiology for tau levels and brain ventricular volume.
Disciplines :
Neurology
Author, co-author :
Jansen, Iris E ; Alzheimer Center Amsterdam, Neurology, Vrije Universiteit Amsterdam, Amsterdam UMC Location VUmc, Amsterdam, The Netherlands. i.e.jansen@vu.nl ; Amsterdam Neuroscience, Neurodegeneration, Amsterdam, The Netherlands. i.e.jansen@vu.nl ; Department of Complex Trait Genetics, Center for Neurogenomics and Cognitive Research, Amsterdam Neuroscience, VU Amsterdam, Amsterdam, The Netherlands. i.e.jansen@vu.nl
van der Lee, Sven J ; Alzheimer Center Amsterdam, Neurology, Vrije Universiteit Amsterdam, Amsterdam UMC Location VUmc, Amsterdam, The Netherlands ; Amsterdam Neuroscience, Neurodegeneration, Amsterdam, The Netherlands ; Section Genomics of Neurodegenerative Diseases and Aging, Human Genetics, Vrije Universiteit Amsterdam, Amsterdam UMC location VUmc, Amsterdam, The Netherlands
Gomez-Fonseca, Duber; Department of Psychiatry, Washington University School of Medicine, St Louis, MO, USA ; NeuroGenomics and Informatics, Washington University School of Medicine, St Louis, MO, USA ; Hope Center for Neurological Disorders, Washington University School of Medicine, St Louis, MO, USA
de Rojas, Itziar ; Research Center and Memory Clinic, Ace Alzheimer Center Barcelona, Universitat Internacional de Catalunya, Barcelona, Spain ; CIBERNED, Network Center for Biomedical Research in Neurodegenerative Diseases, National Institute of Health Carlos III, Madrid, Spain
Dalmasso, Maria Carolina; Division of Neurogenetics and Molecular Psychiatry, Department of Psychiatry and Psychotherapy, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany ; Neurosciences and Complex Systems Unit (ENyS), CONICET, Hospital El Cruce, National University A. Jauretche (UNAJ), Florencio Varela, Argentina
Grenier-Boley, Benjamin; Univ. Lille, Inserm, CHU Lille, Institut Pasteur de Lille, U1167 - RID-AGE / Labex DISTALZ - Facteurs de risque et déterminants moléculaires des maladies liées au vieillissement, F-59000, Lille, France
Zettergren, Anna ; Neuropsychiatric Epidemiology Unit, Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, Centre for Ageing and Health (AGECAP) at the University of Gothenburg, Gothenburg, Sweden
Mishra, Aniket; University of Bordeaux, Inserm, Bordeaux Population Health Research Center, Team VINTAGE, UMR 1219, 33000, Bordeaux, France
Ali, Muhammad ; Department of Psychiatry, Washington University School of Medicine, St Louis, MO, USA ; NeuroGenomics and Informatics, Washington University School of Medicine, St Louis, MO, USA ; Hope Center for Neurological Disorders, Washington University School of Medicine, St Louis, MO, USA
Andrade, Victor; Division of Neurogenetics and Molecular Psychiatry, Department of Psychiatry and Psychotherapy, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany ; Department of Neurodegenerative Diseases and Geriatric Psychiatry, University Hospital Bonn, Medical Faculty, Bonn, Germany
Bellenguez, Céline; Univ. Lille, Inserm, CHU Lille, Institut Pasteur de Lille, U1167 - RID-AGE / Labex DISTALZ - Facteurs de risque et déterminants moléculaires des maladies liées au vieillissement, F-59000, Lille, France
Kleineidam, Luca; Division of Neurogenetics and Molecular Psychiatry, Department of Psychiatry and Psychotherapy, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany ; Department of Neurodegenerative Diseases and Geriatric Psychiatry, University Hospital Bonn, Medical Faculty, Bonn, Germany ; German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany
Küçükali, Fahri ; Complex Genetics of Alzheimer's Disease Group, VIB Center for Molecular Neurology, VIB, Antwerp, Belgium ; Department of Biomedical Sciences, University of Antwerp, Antwerp, Belgium
Sung, Yun Ju; Department of Psychiatry, Washington University School of Medicine, St Louis, MO, USA ; NeuroGenomics and Informatics, Washington University School of Medicine, St Louis, MO, USA ; Hope Center for Neurological Disorders, Washington University School of Medicine, St Louis, MO, USA
Tesí, Niccolo; Alzheimer Center Amsterdam, Neurology, Vrije Universiteit Amsterdam, Amsterdam UMC Location VUmc, Amsterdam, The Netherlands ; Amsterdam Neuroscience, Neurodegeneration, Amsterdam, The Netherlands ; Section Genomics of Neurodegenerative Diseases and Aging, Human Genetics, Vrije Universiteit Amsterdam, Amsterdam UMC location VUmc, Amsterdam, The Netherlands
Vromen, Ellen M ; Alzheimer Center Amsterdam, Neurology, Vrije Universiteit Amsterdam, Amsterdam UMC Location VUmc, Amsterdam, The Netherlands ; Amsterdam Neuroscience, Neurodegeneration, Amsterdam, The Netherlands
Wightman, Douglas P; Department of Complex Trait Genetics, Center for Neurogenomics and Cognitive Research, Amsterdam Neuroscience, VU Amsterdam, Amsterdam, The Netherlands
Alcolea, Daniel ; CIBERNED, Network Center for Biomedical Research in Neurodegenerative Diseases, National Institute of Health Carlos III, Madrid, Spain ; Sant Pau Memory Unit, Department of Neurology, Institut d'Investigacions Biomèdiques Sant Pau - Hospital de Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain
Alegret, Montserrat ; Research Center and Memory Clinic, Ace Alzheimer Center Barcelona, Universitat Internacional de Catalunya, Barcelona, Spain ; CIBERNED, Network Center for Biomedical Research in Neurodegenerative Diseases, National Institute of Health Carlos III, Madrid, Spain
Alvarez, Ignacio; Memory Disorders Unit, Department of Neurology, Hospital Universitari Mutua de Terrassa, Terrassa, Spain ; Fundació per a la Recerca Biomèdica i Social Mútua de Terrassa, Terrassa, Spain
Amouyel, Philippe; Univ. Lille, Inserm, CHU Lille, Institut Pasteur de Lille, U1167 - RID-AGE / Labex DISTALZ - Facteurs de risque et déterminants moléculaires des maladies liées au vieillissement, F-59000, Lille, France
Athanasiu, Lavinia; NORMENT Centre, Institute of Clinical Medicine, University of Oslo and Division of Mental Health, Oslo, Norway
Bahrami, Shahram; NORMENT Centre, Institute of Clinical Medicine, University of Oslo and Division of Mental Health, Oslo, Norway
Bailly, Henri; Université Paris Cité, EA4468, Maladie d'Alzheimer, F-75013 Paris, France
Belbin, Olivia; CIBERNED, Network Center for Biomedical Research in Neurodegenerative Diseases, National Institute of Health Carlos III, Madrid, Spain ; Sant Pau Memory Unit, Department of Neurology, Institut d'Investigacions Biomèdiques Sant Pau - Hospital de Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain
Bergh, Sverre; The Research-Centre for Age-Related Functional Decline and Disease, Innlandet Hospital Trust, Brumunddal, Norway ; Norwegian National Centre for Ageing and Health, Vestfold Hospital Trust, Tønsberg, Norway
Bertram, Lars ; Lübeck Interdisciplinary Platform for Genome Analytics, University of Lübeck, Lübeck, Germany
Biessels, Geert Jan ; Department of Neurology, UMC Utrecht Brain Center, Utrecht, The Netherlands
Blennow, Kaj; Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden ; Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden
Blesa, Rafael; CIBERNED, Network Center for Biomedical Research in Neurodegenerative Diseases, National Institute of Health Carlos III, Madrid, Spain ; Sant Pau Memory Unit, Department of Neurology, Institut d'Investigacions Biomèdiques Sant Pau - Hospital de Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain
Boada, Mercè; Research Center and Memory Clinic, Ace Alzheimer Center Barcelona, Universitat Internacional de Catalunya, Barcelona, Spain ; CIBERNED, Network Center for Biomedical Research in Neurodegenerative Diseases, National Institute of Health Carlos III, Madrid, Spain
Boland, Anne; Université Paris-Saclay, CEA, Centre National de Recherche en Génomique Humaine, 91057, Evry, France
Buerger, Katharina; German Center for Neurodegenerative Diseases (DZNE, Munich), Munich, Germany ; Institute for Stroke and Dementia Research (ISD), University Hospital, LMU Munich, Munich, Germany
Carracedo, Ángel; Grupo de Medicina Xenómica, Centro Nacional de Genotipado (CEGEN-PRB3-ISCIII), Universidade de Santiago de Compostela, Santiago de Compostela, Spain ; Fundación Pública Galega de Medicina Xenómica-CIBERER-IDIS, Santiago de Compostela, Spain
Cervera-Carles, Laura ; CIBERNED, Network Center for Biomedical Research in Neurodegenerative Diseases, National Institute of Health Carlos III, Madrid, Spain ; Sant Pau Memory Unit, Department of Neurology, Institut d'Investigacions Biomèdiques Sant Pau - Hospital de Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain
Chene, Geneviève; University of Bordeaux, Inserm, Bordeaux Population Health Research Center, Team VINTAGE, UMR 1219, 33000, Bordeaux, France ; Department of Neurology, CHU de Bordeaux, 33000, Bordeaux, France
Claassen, Jurgen A H R ; Radboudumc Alzheimer Center, Department of Geriatrics, Radboud University Medical Center, Nijmegen, The Netherlands ; Donders Center for Medical Neuroscience, Nijmegen, The Netherlands
Debette, Stephanie; University of Bordeaux, Inserm, Bordeaux Population Health Research Center, Team VINTAGE, UMR 1219, 33000, Bordeaux, France ; Department of Neurology, CHU de Bordeaux, 33000, Bordeaux, France ; Department of Neurology, Boston University School of Medicine, Boston, MA, 2115, USA
Deleuze, Jean-Francois; Université Paris-Saclay, CEA, Centre National de Recherche en Génomique Humaine, 91057, Evry, France
de Deyn, Peter Paul ; Department of Neurology and Alzheimer Center Groningen, University Medical Center Groningen, Groningen, The Netherlands
Diehl-Schmid, Janine; Center for Cognitive Disorders, Department of Psychiatry and Psychotherapy, Klinikum rechts der Isar, Technical University of Munich, School of Medicine, Munich, Germany ; kbo-Inn-Salzach-Hospital, Wasserburg am Inn, Germany
Djurovic, Srdjan ; Department of Medical Genetics, Oslo University Hospital, Oslo, Norway ; Department of Clinical Science, NORMENT Centre, University of Bergen, Bergen, Norway
Dols-Icardo, Oriol; CIBERNED, Network Center for Biomedical Research in Neurodegenerative Diseases, National Institute of Health Carlos III, Madrid, Spain ; Sant Pau Memory Unit, Department of Neurology, Institut d'Investigacions Biomèdiques Sant Pau - Hospital de Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain
Dufouil, Carole; University of Bordeaux, Inserm, Bordeaux Population Health Research Center, Team VINTAGE, UMR 1219, 33000, Bordeaux, France ; Pôle de Santé Publique Centre Hospitalier Universitaire (CHU) de Bordeaux, Bordeaux, France
Duron, Emmanuelle; Univerisité Paris-Saclay. Inserm 1178 MOODS, Paris, France
Düzel, Emrah; German Center for Neurodegenerative Diseases (DZNE), Magdeburg, Germany ; Institute of Cognitive Neurology and Dementia Research (IKND), Otto-von-Guericke University, Magdeburg, Germany
EADB consortium
Fladby, Tormod; Institute of Clinical Medicine, University of Oslo, Oslo, Norway ; Department of Neurology, Akershus University Hospital, Lorenskog, Norway
Fortea, Juan; CIBERNED, Network Center for Biomedical Research in Neurodegenerative Diseases, National Institute of Health Carlos III, Madrid, Spain ; Sant Pau Memory Unit, Department of Neurology, Institut d'Investigacions Biomèdiques Sant Pau - Hospital de Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain
Frölich, Lutz; Department of Geriatric Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg, Germany
García-González, Pablo ; Research Center and Memory Clinic, Ace Alzheimer Center Barcelona, Universitat Internacional de Catalunya, Barcelona, Spain ; CIBERNED, Network Center for Biomedical Research in Neurodegenerative Diseases, National Institute of Health Carlos III, Madrid, Spain
Garcia-Martinez, Maria; Cognitive Impairment Unit, Neurology Service, "Marqués de Valdecilla" University Hospital, Institute for Research "Marques de Valdecilla" (IDIVAL), University of Cantabria, Santander, Spain, and Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain
Giegling, Ina; Division of General Psychiatry, Department of Psychiatry and Psychotherapy, Medical University of Vienna, Vienna, Austria
Goldhardt, Oliver; Center for Cognitive Disorders, Department of Psychiatry and Psychotherapy, Klinikum rechts der Isar, Technical University of Munich, School of Medicine, Munich, Germany
Gobom, Johan; Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden
Grimmer, Timo; Center for Cognitive Disorders, Department of Psychiatry and Psychotherapy, Klinikum rechts der Isar, Technical University of Munich, School of Medicine, Munich, Germany
Haapasalo, Annakaisa; A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland
Hampel, Harald; Alzheimer Precision Medicine (APM), Sorbonne University, AP-HP, Pitié-Salpêtrière Hospital, Paris, France ; Neurology Business Group, Eisai Inc, 100 Tice Blvd, Woodcliff Lake, NJ, 07677, USA
Hanon, Olivier; Université Paris Cité, EA4468, Maladie d'Alzheimer, F-75013 Paris, France ; Service gériatrie, Centre Mémoire de Ressources et Recherches Ile de France-Broca, AP-HP, Hôpital Broca, F-75013, Paris, France
Hausner, Lucrezia; Department of Geriatric Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg, Germany
Heilmann-Heimbach, Stefanie; Institute of Human Genetics, University of Bonn, School of Medicine and University Hospital Bonn, 53127, Bonn, Germany
Helisalmi, Seppo; Institute of Clinical Medicine, Internal Medicine, University of Eastern Finland, Kuopio, Finland
HENEKA, Michael ; Department of Neurodegenerative Diseases and Geriatric Psychiatry, University Hospital Bonn, Medical Faculty, Bonn, Germany ; German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany
Hernández, Isabel; Research Center and Memory Clinic, Ace Alzheimer Center Barcelona, Universitat Internacional de Catalunya, Barcelona, Spain ; CIBERNED, Network Center for Biomedical Research in Neurodegenerative Diseases, National Institute of Health Carlos III, Madrid, Spain
Herukka, Sanna-Kaisa; Department of Neurology, Institute of Clinical Medicine, University of Eastern Finland, Kuopio, Finland
Holstege, Henne; Alzheimer Center Amsterdam, Neurology, Vrije Universiteit Amsterdam, Amsterdam UMC Location VUmc, Amsterdam, The Netherlands ; Amsterdam Neuroscience, Neurodegeneration, Amsterdam, The Netherlands ; Section Genomics of Neurodegenerative Diseases and Aging, Human Genetics, Vrije Universiteit Amsterdam, Amsterdam UMC location VUmc, Amsterdam, The Netherlands
Jarholm, Jonas; Department of Neurology, Akershus University Hospital, Lorenskog, Norway
Kern, Silke; Neuropsychiatric Epidemiology Unit, Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, Centre for Ageing and Health (AGECAP) at the University of Gothenburg, Gothenburg, Sweden ; Region Västra Götaland, Sahlgrenska University Hospital, Psychiatry, Cognition and Old Age Psychiatry Clinic, Gothenburg, Sweden
Knapskog, Anne-Brita; Department of Geriatric Medicine, Oslo University Hospital, Oslo, Norway
Koivisto, Anne M; Department of Neurology, Institute of Clinical Medicine, University of Eastern Finland, Kuopio, Finland ; Department of Neurology, Kuopio University Hospital, Kuopio, Finland ; Department of Neurology, Helsinki University Hospital, Helsinki, Finland
Kornhuber, Johannes ; Department of Psychiatry and Psychotherapy, Universitätsklinikum Erlangen, and Friedrich-Alexander Universität Erlangen-Nürnberg, Erlangen, Germany
Kuulasmaa, Teemu; Bioinformatics Center, Institute of Biomedicine, University of Eastern Finland, Kuopio, Finland
Lage, Carmen; Cognitive Impairment Unit, Neurology Service, "Marqués de Valdecilla" University Hospital, Institute for Research "Marques de Valdecilla" (IDIVAL), University of Cantabria, Santander, Spain, and Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain ; Atlantic Fellow at the Global Brain Health Institute (GBHI) -, University of California, San Francisco, USA
Laske, Christoph; German Center for Neurodegenerative Diseases (DZNE), Tübingen, Germany ; Section for Dementia Research, Hertie Institute for Clinical Brain Research and Department of Psychiatry and Psychotherapy, University of Tübingen, Tübingen, Germany
Leinonen, Ville ; Institute of Clinical Medicine, Neurosurgery, University of Eastern Finland, Kuopio, Finland ; Department of Neurosurgery, Kuopio University Hospital, Kuopio, Finland
Lewczuk, Piotr ; Department of Psychiatry and Psychotherapy, Universitätsklinikum Erlangen, and Friedrich-Alexander Universität Erlangen-Nürnberg, Erlangen, Germany ; Department of Neurodegeneration Diagnostics, Medical University of Białystok, Białystok, Poland
Lleó, Alberto; CIBERNED, Network Center for Biomedical Research in Neurodegenerative Diseases, National Institute of Health Carlos III, Madrid, Spain ; Sant Pau Memory Unit, Department of Neurology, Institut d'Investigacions Biomèdiques Sant Pau - Hospital de Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain
de Munain, Adolfo López; CIBERNED, Network Center for Biomedical Research in Neurodegenerative Diseases, National Institute of Health Carlos III, Madrid, Spain ; Hospital Universitario Donostia-OSAKIDETZA, Donostia, Spain ; Instituto Biodonostia, San Sebastián, Spain ; University of The Basque Country, San Sebastian, Spain
Lopez-Garcia, Sara; Cognitive Impairment Unit, Neurology Service, "Marqués de Valdecilla" University Hospital, Institute for Research "Marques de Valdecilla" (IDIVAL), University of Cantabria, Santander, Spain, and Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain
Maier, Wolfgang; Department of Neurodegenerative Diseases and Geriatric Psychiatry, University Hospital Bonn, Medical Faculty, Bonn, Germany
Marquié, Marta ; Research Center and Memory Clinic, Ace Alzheimer Center Barcelona, Universitat Internacional de Catalunya, Barcelona, Spain ; CIBERNED, Network Center for Biomedical Research in Neurodegenerative Diseases, National Institute of Health Carlos III, Madrid, Spain
Mol, Merel O ; Department of Neurology and Alzheimer Center Erasmus MC, Erasmus MC University Medical Center, Rotterdam, The Netherlands
Montrreal, Laura; Research Center and Memory Clinic, Ace Alzheimer Center Barcelona, Universitat Internacional de Catalunya, Barcelona, Spain
Moreno, Fermin; CIBERNED, Network Center for Biomedical Research in Neurodegenerative Diseases, National Institute of Health Carlos III, Madrid, Spain ; Hospital Universitario Donostia-OSAKIDETZA, Donostia, Spain ; Instituto Biodonostia, San Sebastián, Spain
Moreno-Grau, Sonia; Research Center and Memory Clinic, Ace Alzheimer Center Barcelona, Universitat Internacional de Catalunya, Barcelona, Spain ; CIBERNED, Network Center for Biomedical Research in Neurodegenerative Diseases, National Institute of Health Carlos III, Madrid, Spain
Nicolas, Gael; Department of Genetics and CNR-MAJ, Normandie Univ, UNIROUEN, Inserm U1245 and CHU Rouen, Rouen, France
Nöthen, Markus M; Institute of Human Genetics, University of Bonn, School of Medicine and University Hospital Bonn, 53127, Bonn, Germany
Orellana, Adelina; Research Center and Memory Clinic, Ace Alzheimer Center Barcelona, Universitat Internacional de Catalunya, Barcelona, Spain ; CIBERNED, Network Center for Biomedical Research in Neurodegenerative Diseases, National Institute of Health Carlos III, Madrid, Spain
Pålhaugen, Lene; Institute of Clinical Medicine, University of Oslo, Oslo, Norway ; Department of Neurology, Akershus University Hospital, Lorenskog, Norway
Papma, Janne M; Department of Neurology and Alzheimer Center Erasmus MC, Erasmus MC University Medical Center, Rotterdam, The Netherlands
Pasquier, Florence ; Univ. Lille, Inserm, CHU Lille, Institut Pasteur de Lille, U1167 - RID-AGE / Labex DISTALZ - Facteurs de risque et déterminants moléculaires des maladies liées au vieillissement, F-59000, Lille, France
Perneczky, Robert; German Center for Neurodegenerative Diseases (DZNE, Munich), Munich, Germany ; Department of Psychiatry and Psychotherapy, University Hospital, LMU Munich, Munich, Germany ; Munich Cluster for Systems Neurology (SyNergy) Munich, Munich, Germany ; Ageing Epidemiology Research Unit, School of Public Health, Imperial College London, London, UK
Peters, Oliver; German Center for Neurodegenerative Diseases (DZNE), Magdeburg, Germany ; German Center for Neurodegenerative Diseases (DZNE), Berlin, Germany
Pijnenburg, Yolande A L; Alzheimer Center Amsterdam, Neurology, Vrije Universiteit Amsterdam, Amsterdam UMC Location VUmc, Amsterdam, The Netherlands ; Amsterdam Neuroscience, Neurodegeneration, Amsterdam, The Netherlands
Popp, Julius ; Department of Geriatric Psychiatry, University Hospital of Psychiatry Zürich and University of Zürich, Zurich, Switzerland ; Old Age Psychiatry, Department of Psychiatry, University Hospital of Lausanne, Lausanne, Switzerland
Posthuma, Danielle; Department of Complex Trait Genetics, Center for Neurogenomics and Cognitive Research, Amsterdam Neuroscience, VU Amsterdam, Amsterdam, The Netherlands
Pozueta, Ana; Cognitive Impairment Unit, Neurology Service, "Marqués de Valdecilla" University Hospital, Institute for Research "Marques de Valdecilla" (IDIVAL), University of Cantabria, Santander, Spain, and Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain
Priller, Josef; German Center for Neurodegenerative Diseases (DZNE), Berlin, Germany ; Department of Psychiatry and Psychotherapy, Charité, Charitéplatz 1, 10117, Berlin, Germany ; Department of Psychiatry and Psychotherapy, Klinikum rechts der isar, Technical University Munich, 81675, Munich, Germany
Puerta, Raquel; Research Center and Memory Clinic, Ace Alzheimer Center Barcelona, Universitat Internacional de Catalunya, Barcelona, Spain
Quintela, Inés ; Grupo de Medicina Xenómica, Centro Nacional de Genotipado (CEGEN-PRB3-ISCIII), Universidade de Santiago de Compostela, Santiago de Compostela, Spain
Ramakers, Inez; Department of Psychiatry and Neuropsychologie, Alzheimer Center Limburg, Maastricht University, Maastricht, The Netherlands
Rodriguez-Rodriguez, Eloy ; Cognitive Impairment Unit, Neurology Service, "Marqués de Valdecilla" University Hospital, Institute for Research "Marques de Valdecilla" (IDIVAL), University of Cantabria, Santander, Spain, and Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain
Rujescu, Dan; Division of General Psychiatry, Department of Psychiatry and Psychotherapy, Medical University of Vienna, Vienna, Austria
Saltvedt, Ingvild; Department of Neuromedicine and Movement Science, Norwegian University of Science and Technology (NTNU), Trondheim, Norway ; Department of Geriatrics, St Olav Hospital, University Hospital of Trondheim, Trondheim, Norway
Scheltens, Philip; Alzheimer Center Amsterdam, Neurology, Vrije Universiteit Amsterdam, Amsterdam UMC Location VUmc, Amsterdam, The Netherlands ; Amsterdam Neuroscience, Neurodegeneration, Amsterdam, The Netherlands
Scherbaum, Norbert; Department of Psychiatry and Psychotherapy, Medical Faculty, LVR-Hospital Essen, University of Duisburg-Essen, Essen, Germany
Schmid, Matthias; Institute of Medical Biometry, Informatics and Epidemiology, University Hospital of Bonn, Bonn, Germany
Schneider, Anja; Department of Neurodegenerative Diseases and Geriatric Psychiatry, University Hospital Bonn, Medical Faculty, Bonn, Germany ; German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany
Selbæk, Geir ; Norwegian National Centre for Ageing and Health, Vestfold Hospital Trust, Tønsberg, Norway ; Institute of Clinical Medicine, University of Oslo, Oslo, Norway ; Department of Geriatric Medicine, Oslo University Hospital, Oslo, Norway
Selnes, Per; Department of Neurology, Akershus University Hospital, Lorenskog, Norway
Shadrin, Alexey; NORMENT Centre, Institute of Clinical Medicine, University of Oslo and Division of Mental Health, Oslo, Norway
Skoog, Ingmar; Neuropsychiatric Epidemiology Unit, Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, Centre for Ageing and Health (AGECAP) at the University of Gothenburg, Gothenburg, Sweden ; Region Västra Götaland, Sahlgrenska University Hospital, Psychiatry, Cognition and Old Age Psychiatry Clinic, Gothenburg, Sweden
Soininen, Hilkka; Department of Neurology, Institute of Clinical Medicine, University of Eastern Finland, Kuopio, Finland
Tárraga, Lluís; Research Center and Memory Clinic, Ace Alzheimer Center Barcelona, Universitat Internacional de Catalunya, Barcelona, Spain ; CIBERNED, Network Center for Biomedical Research in Neurodegenerative Diseases, National Institute of Health Carlos III, Madrid, Spain
Teipel, Stefan; German Center for Neurodegenerative Diseases (DZNE), Rostock, Germany ; Department of Psychosomatic Medicine, Rostock University Medical Center, Gehlsheimer Str. 20, 18147, Rostock, Germany
GR@ACE study group
Tijms, Betty ; Alzheimer Center Amsterdam, Neurology, Vrije Universiteit Amsterdam, Amsterdam UMC Location VUmc, Amsterdam, The Netherlands ; Amsterdam Neuroscience, Neurodegeneration, Amsterdam, The Netherlands
Tsolaki, Magda; 1st Department of Neurology, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, Thessaloniki, Makedonia, Greece
Van Broeckhoven, Christine; Department of Biomedical Sciences, University of Antwerp, Antwerp, Belgium ; Neurodegenerative Brain Diseases Group, VIB Center for Molecular Neurology, VIB, Antwerp, Belgium
Van Dongen, Jasper ; Complex Genetics of Alzheimer's Disease Group, VIB Center for Molecular Neurology, VIB, Antwerp, Belgium ; Department of Biomedical Sciences, University of Antwerp, Antwerp, Belgium
van Swieten, John C; Department of Neurology and Alzheimer Center Erasmus MC, Erasmus MC University Medical Center, Rotterdam, The Netherlands
Vandenberghe, Rik; Neurology, University Hospitals Leuven, Leuven, Belgium ; Laboratory for Cognitive Neurology, Department of Neurosciences, Leuven Brain Institute, Leuven, Belgium
Vidal, Jean-Sébastien; Université Paris Cité, EA4468, Maladie d'Alzheimer, F-75013 Paris, France
Visser, Pieter J; Alzheimer Center Amsterdam, Neurology, Vrije Universiteit Amsterdam, Amsterdam UMC Location VUmc, Amsterdam, The Netherlands ; Amsterdam Neuroscience, Neurodegeneration, Amsterdam, The Netherlands ; Alzheimer Center Limburg, School for Mental Health and Neuroscience Maastricht University, Maastricht, The Netherlands ; Department of Neurobiology, Care Sciences and Society, Division of Neurogeriatrics Karolinska Institutet, Stockholm, Sweden
Vogelgsang, Jonathan; Department of Psychiatry and Psychotherapy, University Medical Center Goettingen, Göttingen, Germany ; Department of Psychiatry, Harvard Medical School, McLean Hospital, Belmont, MA, USA
Waern, Margda ; Neuropsychiatric Epidemiology Unit, Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, Centre for Ageing and Health (AGECAP) at the University of Gothenburg, Gothenburg, Sweden ; Region Västra Götaland, Sahlgrenska University Hospital, Psychiatry, Psychosis Clinic, Gothenburg, Sweden
Wagner, Michael ; Department of Neurodegenerative Diseases and Geriatric Psychiatry, University Hospital Bonn, Medical Faculty, Bonn, Germany ; German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany
Wiltfang, Jens; Department of Psychiatry and Psychotherapy, University Medical Center Goettingen, Göttingen, Germany ; German Center for Neurodegenerative Diseases (DZNE), Göttingen, Germany ; Medical Science Department, iBiMED, Aveiro, Portugal
Wittens, Mandy M J; Department of Biomedical Sciences, University of Antwerp, Antwerp, Belgium ; Center for Neurosciences (C4N), Vrije Universiteit Brussel, Brussels, Belgium
Zetterberg, Henrik ; Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden ; Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden ; Department of Neurodegenerative Disease, UCL Institute of Neurology, London, UK ; UK Dementia Research Institute at UCL, London, UK ; Hong Kong Center for Neurodegenerative Diseases, Hong Kong, China
Zulaica, Miren; CIBERNED, Network Center for Biomedical Research in Neurodegenerative Diseases, National Institute of Health Carlos III, Madrid, Spain ; Hospital Universitario Donostia-OSAKIDETZA, Donostia, Spain ; Instituto Biodonostia, San Sebastián, Spain
van Duijn, Cornelia M ; Department of Epidemiology, ErasmusMC, Rotterdam, The Netherlands ; Nuffield Department of Population Health, Oxford University, Oxford, UK
Bjerke, Maria; Department of Biomedical Sciences, University of Antwerp, Antwerp, Belgium ; Center for Neurosciences (C4N), Vrije Universiteit Brussel, Brussels, Belgium ; Laboratory of Neurochemistry, Universitair Ziekenhuis Brussel, Brussels, Belgium
Engelborghs, Sebastiaan ; Department of Biomedical Sciences, University of Antwerp, Antwerp, Belgium ; Center for Neurosciences (C4N), Vrije Universiteit Brussel, Brussels, Belgium ; Laboratory of Neurochemistry, Universitair Ziekenhuis Brussel, Brussels, Belgium ; Department of Neurology, Universitair Ziekenhuis Brussel, Brussels, Belgium
Jessen, Frank; German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany ; Department of Psychiatry and Psychotherapy, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany ; Cluster of Excellence Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany
Teunissen, Charlotte E; Amsterdam Neuroscience, Neurodegeneration, Amsterdam, The Netherlands ; Neurochemistry Lab, Department of Clinical Chemistry, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam UMC, Amsterdam, The Netherlands
Pastor, Pau; Unit of Neurodegenerative diseases, Department of Neurology, University Hospital Germans Trias i Pujol and The Germans Trias i Pujol Research Institute (IGTP) Badalona, Barcelona, Spain
Hiltunen, Mikko; Institute of Biomedicine, University of Eastern Finland, Kuopio, Finland
Ingelsson, Martin; Department of Public Health and Caring Sciences, Molecular Geriatrics, Rudbeck Laboratory, Uppsala University, Uppsala, Sweden ; Krembil Brain Institute, University Health Network, Toronto, Ontario, Canada ; Department of Medicine and Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto, Toronto, Canada
Andreassen, Ole A ; NORMENT Centre, Institute of Clinical Medicine, University of Oslo and Division of Mental Health, Oslo, Norway ; Addiction, Oslo University Hospital, 0407, Oslo, Norway
Clarimón, Jordi; CIBERNED, Network Center for Biomedical Research in Neurodegenerative Diseases, National Institute of Health Carlos III, Madrid, Spain ; Sant Pau Memory Unit, Department of Neurology, Institut d'Investigacions Biomèdiques Sant Pau - Hospital de Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain
Sleegers, Kristel ; Complex Genetics of Alzheimer's Disease Group, VIB Center for Molecular Neurology, VIB, Antwerp, Belgium ; Department of Biomedical Sciences, University of Antwerp, Antwerp, Belgium
Ruiz, Agustín; Research Center and Memory Clinic, Ace Alzheimer Center Barcelona, Universitat Internacional de Catalunya, Barcelona, Spain ; CIBERNED, Network Center for Biomedical Research in Neurodegenerative Diseases, National Institute of Health Carlos III, Madrid, Spain
Ramirez, Alfredo ; Division of Neurogenetics and Molecular Psychiatry, Department of Psychiatry and Psychotherapy, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany ; Department of Neurodegenerative Diseases and Geriatric Psychiatry, University Hospital Bonn, Medical Faculty, Bonn, Germany ; German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany ; Cluster of Excellence Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany ; Department of Psychiatry, Glenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases, San Antonio, TX, USA
Cruchaga, Carlos ; Department of Psychiatry, Washington University School of Medicine, St Louis, MO, USA ; NeuroGenomics and Informatics, Washington University School of Medicine, St Louis, MO, USA ; Hope Center for Neurological Disorders, Washington University School of Medicine, St Louis, MO, USA
Lambert, Jean-Charles; Univ. Lille, Inserm, CHU Lille, Institut Pasteur de Lille, U1167 - RID-AGE / Labex DISTALZ - Facteurs de risque et déterminants moléculaires des maladies liées au vieillissement, F-59000, Lille, France
van der Flier, Wiesje ; Alzheimer Center Amsterdam, Neurology, Vrije Universiteit Amsterdam, Amsterdam UMC Location VUmc, Amsterdam, The Netherlands. wm.vdflier@amsterdamumc.nl ; Amsterdam Neuroscience, Neurodegeneration, Amsterdam, The Netherlands. wm.vdflier@amsterdamumc.nl
EU Joint Programme – Neurodegenerative Disease Research
Funding text :
This work was supported by a grant (European Alzheimer DNA BioBank, EADB) from the EU Joint Programme, Neurodegenerative Disease Research (JPND). Amsterdam dementia Cohort (ADC): Research of the Alzheimer center Amsterdam is part of the neurodegeneration research program of Amsterdam Neuroscience. The Alzheimer Center Amsterdam is supported by Stichting Alzheimer Nederland and Stichting VUmc fonds. The clinical database structure was developed with funding from Stichting Dioraphte. Genotyping of the Dutch case-control samples was performed in the context of EADB (European Alzheimer DNA biobank) funded by the JPco-fuND FP-829-029 (ZonMW projectnumber 733051061).Part of the work described in this study was carried out in the context of the Parelsnoer Institute (PSI). PSI was part of and funded by the Dutch Federation of University Medical Centers and has received initial funding from the Dutch Government (from 2007-2011). Since 2020, this work was carried out in the context of Parelsnoer clinical biobanks at Health-RI ( https://www.health-ri.nl/initiatives/parelsnoer ). Part of the genotyping included in this work was funded by the JPND EADB grant (German Federal Ministry of Education and Research (BMBF) grant: 01ED1619A). Alfredo Ramirez is also supported by the German Research Foundation (DFG) grants Nr: RA 1971/6-1, RA1971/7-1, and RA 1971/8-1. We would like to thank patients and controls who participated in this project. The Genome Research @ Fundació ACE project (GR@ACE) is supported by Grifols SA, Fundación bancaria ‘La Caixa’, Fundació ACE, and CIBERNED. A.R. and M.B. receive support from the European Union/EFPIA Innovative Medicines Initiative Joint undertaking ADAPTED and MOPEAD projects (grant numbers 115975 and 115985, respectively). M.B. and A.R. are also supported by national grants PI13/02434, PI16/01861, PI17/01474, PI19/01240 and PI19/01301. Acción Estratégica en Salud is integrated into the Spanish National R + D + I Plan and funded by ISCIII (Instituto de Salud Carlos III)–Subdirección General de Evaluación and the Fondo Europeo de Desarrollo Regional (FEDER–‘Una manera de hacer Europa’). The position held by I.dR. is funded by grant. FI20/00215. PFIS Contratos Predoctorales de Formación en Investigación en Salud. We would like to thank UCL Genomics, London, UK, for performing the genotyping analyses of the samples within the Gothenburg H70 Birth Cohort Studies and Clinical AD Sweden. The recruitment and clinical characterization of research participants at Washington University were supported by NIH P30AG066444, and P01AG003991. This work was supported by access to equipment made possible by the Hope Center for Neurological Disorders, the Neurogenomics and Informatics Center (NGI: https://neurogenomics.wustl.edu/)and the Departments of Neurology and Psychiatry at Washington University School of Medicine. Research at the Belgian EADB site is funded in part by the Alzheimer Research Foundation (SAO-FRA), The Research Foundation Flanders (FWO), and the University of Antwerp Research Fund. FK is supported by a BOF DOCPRO fellowship of the University of Antwerp Research Fund. The work of Valdecilla was supported by grants from the Instituto de Salud Carlos III (Fondo de Investigación Sanitario, PI08/0139, PI12/02288, PI16/01652, and PI20/01011), the JPND (DEMTEST PI11/03028), the CIBERNED, and the Siemens Healthineers. We thank the Valdecilla Biobank (PT17/0015/0019), integrated into the Spanish Biobank Network, for their support and collaboration in sample collection and management. Our heartfelt thanks to the participants of the Valdecilla Cohort for their generosity. The work of ADGEN was supported by EU Joint Programme—Neurodegenerative Disease Research (301220) and the Academy of Finland (338182). The DELCODE study (Study-ID:BN012 ) was supported and conducted by the German Center for Neurodegenerative Diseases (DZNE). The data samples were provided by the DELCODE study group. Details and participating sites can be found at www.dzne.de/en/research/studies/clinical-studies/delcode . The German Dementia Competence Network (KND) is funded by the German Federal Ministry of Education and Research (BMBF) grants Number: 01G10102, 01GI0420, 01GI0422, 01GI0423, 01GI0429, 01GI0431, 01GI0433, 04GI0434, 01GI0711. WF, SvdL, HHolstege, CT and PhS are recipients of ABOARD, which is a public-private partnership receiving funding from ZonMW (#73305095007) and Health~Holland, Topsector Life Sciences & Health (PPP-allowance; #LSHM20106). More than 30 partners participate in ABOARD ( www.aboard-project.nl ). ABOARD also receives funding from de Hersenstichting, Edwin Bouw Fonds and Gieskes-Strijbisfonds. IEJ was partially supported by NWO Gravitation program BRAINSCAPES: A Roadmap from Neurogenetics to Neurobiology (NWO: 024.004.012). AZ was supported by the Swedish Alzheimer Foundation (AF-939988, AF-930582, AF-646061, AF-741361), and the Dementia Foundation (2020-04-13, 2021-04-17). ISk was supported by the Swedish state under the agreement between the Swedish government and the county councils, the ALF-agreement (ALF 716681), the Swedish Research Council (no 11267, 825-2012-5041, 2013-8717, 2015-02830, 2017-00639, 2019-01096), Swedish Research Council for Health, Working Life and Welfare (no 2001-2646, 2001-2835, 2001-2849, 2003-0234, 2004-0150, 2005-0762, 2006-0020, 2008-1229, 2008-1210, 2012-1138, 2004-0145, 2006-0596, 2008-1111, 2010-0870, 2013-1202, 2013-2300, 2013-2496), Swedish Brain Power, Hjärnfonden, Sweden (FO2016-0214, FO2018-0214, FO2019- 0163), the Alzheimer's Association Zenith Award (ZEN-01-3151), the Alzheimer's Association Stephanie B. Overstreet Scholars (IIRG-00-2159), the Alzheimer's Association (IIRG-03-6168, IIRG-09-131338) and the Bank of Sweden Tercentenary Foundation. SK was supported by the Swedish state under the agreement between the Swedish government and the county councils, the ALF-agreement (ALFGBG-81392, ALF GBG-771071), the Swedish Alzheimer Foundation (AF-842471, AF-737641, AF-939825), and the Swedish Research Council (2019-02075). MW was supported by the Swedish Research Council 2016-01590. DP was supported by BRAINSCAPES: A Roadmap from Neurogenetics to Neurobiology (grant no. 024.004.012), and a European Research Council advanced grant (Grant No, ERC-2018-AdG GWAS2FUNC 834057. HZ is a Wallenberg Scholar supported by grants from the Swedish Research Council (2018-02532), the European Research Council (681712), Swedish State Support for Clinical Research (ALFGBG-720931), the Alzheimer Drug Discovery Foundation (ADDF), USA (201809-2016862), the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No 860197 (MIRIADE), and the UK Dementia Research Institute at UCL. KB was supported by the Swedish Research Council (#2017-00915), the Alzheimer Drug Discovery Foundation (ADDF), USA (#RDAPB-201809-2016615), the Swedish Alzheimer Foundation (#AF-742881), Hjärnfonden, Sweden (#FO2017-0243), the Swedish state under the agreement between the Swedish government and the County Councils, the ALF-agreement (#ALFGBG-715986), the European Union Joint Program for Neurodegenerative Disorders (JPND2019-466-236), the National Institute of Health (NIH), USA, (grant #1R01AG068398-01), and the Alzheimer’s Association 2021 Zenith Award (ZEN-21-848495). CC receives support from the National Institutes of Health (R01AG044546, R01AG064877, RF1AG053303, R01AG058501, U01AG058922, RF1AG058501, R01AG064614), and the Chuck Zuckerberg Initiative (CZI).Research programs of Wiesje van der Flier have been funded by ZonMW, NWO, EU-FP7, EU-JPND, Alzheimer Nederland, CardioVascular Onderzoek Nederland, Health ~ Holland, Topsector Life Sciences & Health, stichting Dioraphte, Gieskes-Strijbis fonds, stichting Equilibrio, Pasman stichting, stichting Alzheimer & Neuropsychiatrie Foundation, Biogen MA Inc, Boehringer Ingelheim, Life-MI, AVID, Roche BV, Fujifilm, Combinostics. WF holds the Pasman chair. WF is recipient of ABOARD, which is a public–private partnership receiving funding from ZonMW (#73305095007) and Health ~ Holland, Topsector Life Sciences & Health (PPP-allowance; #LSHM20106). WF has performed contract research for Biogen MA Inc, and Boehringer Ingelheim. WF has been an invited speaker at Boehringer Ingelheim, Biogen MA Inc, Danone, Eisai, WebMD Neurology (Medscape), Springer Healthcare. WF is consultant to Oxford Health Policy Forum CIC, Roche, and Biogen MA Inc. WF participated in advisory boards of Biogen MA Inc and Roche. All funding is paid to her institution. WF was associate editor of Alzheimer, Research & Therapy in 2020/2021. WF is associate editor at Brain. CC receives research support from: Biogen, EISAI, Alector and Parabon. The funders of the study had no role in the collection, analysis, or interpretation of data; in the writing of the report; or in the decision to submit the paper for publication. CC is a member of the advisory board of Vivid genetics, Halia Therapeutics and ADx Healthcare. HZ has served at scientific advisory boards for Denali, Roche Diagnostics, Wave, Samumed, Siemens Healthineers, Pinteon Therapeutics and CogRx, has given lectures in symposia sponsored by Fujirebio, Alzecure and Biogen, and is a co-founder of Brain Biomarker Solutions in Gothenburg AB (BBS), which is a part of the GU Ventures Incubator Program (outside submitted work). KBlennow has served as a consultant, at advisory boards, or at data monitoring committees for Abcam, Axon, Biogen, JOMDD/Shimadzu. Julius Clinical, Lilly, MagQu, Novartis, Roche Diagnostics, and Siemens Healthineers, and is a co-founder of Brain Biomarker Solutions in Gothenburg AB (BBS), which is a part of the GU Ventures Incubator Program. OAA is a consultant to HealthLytix, and received speaker’s honorarium from Lundbeck and Sunovion. SE has served at scientific advisory boards for Biogen, Danone, Eisai, icometrix, Pfizer, Novartis, Nutricia, Roche and has received unrestricted research grants from ADx Neurosciences and Janssen Pharmaceutica. CC receives research support from: Biogen, EISAI, Alector, GSK and Parabon. The funders of the study had no role in the collection, analysis, or interpretation of data; in the writing of the report; or in the decision to submit the paper for publication. CC is a member of the advisory board of Vivid genetics, Halia Therapeutics and ADx Healthcare. HHampel is an employee of Eisai Inc. and serves as Senior Associate Editor for the Journal Alzheimer’s & Dementia; during the past three years he had received lecture fees from Servier, Biogen and Roche, research grants from Pfizer, Avid, and MSD Avenir (paid to the institution), travel funding from Eisai, Functional Neuromodulation, Axovant, Eli Lilly and company, Takeda and Zinfandel, GE-Healthcare and Oryzon Genomics, consultancy fees from Qynapse, Jung Diagnostics, Cytox Ltd., Axovant, Anavex, Takeda and Zinfandel, GE Healthcare, Oryzon Genomics, and Functional Neuromodulation, and participated in scientific advisory boards of Functional Neuromodulation, Axovant, Eisai, Eli Lilly and company, Cytox Ltd., GE Healthcare, Takeda and Zinfandel, Oryzon Genomics and Roche Diagnostics. DA participated in advisory boards from Fujirebio-Europe and Roche Diagnostics and received speaker honoraria from Fujirebio-Europe, Roche Diagnostics, Nutricia, Krka Farmacéutica S.L., Zambon S.A.U. and Esteve Pharmaceuticals S.A. OG reports consulting fees from Eli Lilly, grants to his institution from Actelion, and prescreening activities for Julius Clinical/Toyama. ABK has been a PI in the drug trials Roche BN29553, Boehringer-Ingelheim 1346.0023 and is PI in Novo Nordisk NN6535-4730. AL has received personal fees for advisory board services and/or speaker honoraria from Fujirebio-Europe, Roche Diagnostics, Nutricia,Krka Farmacéutica SL, Biogen and Zambon. PSJ has received personal fees for advisory board from Roche Diagnostics and Zambon. GS participated in one advisory board meeting from Biogen. MI is a paid consultant to BioArctic AB. KS is editor at Acta Neuropathologica and associate editor at Alzheimer’s Research & Therapy. HZ has served at scientific advisory boards for Denali, Roche Diagnostics, Wave, Samumed, Siemens Healthineers, Pinteon Therapeutics and CogRx, has given lectures in symposia sponsored by Fujirebio, Alzecure and Biogen, and is a co-founder of Brain Biomarker Solutions in Gothenburg AB (BBS), which is a part of the GU Ventures Incubator Program (outside submitted work). All other authors declare no financial interests or potential conflicts of interest.
The Gene Ontology resource: enriching a GOld mine. Nucleic Acids Res 49:D325–D334. https://doi.org/10.1093/nar/gkaa1113
Alcolea D, Martínez-Lage P, Sánchez-Juan P, Olazarán J, Antúnez C, Izagirre A et al (2015) Amyloid precursor protein metabolism and inflammation markers in preclinical Alzheimer disease. Neurology 85:626–633. 10.1212/wnl.0000000000001859 DOI: 10.1212/wnl.0000000000001859
Alcolea D, Pegueroles J, Muñoz L, Camacho V, López-Mora D, Fernández-León A et al (2019) Agreement of amyloid PET and CSF biomarkers for Alzheimer’s disease on Lumipulse. Ann Clin Transl Neurol 6:1815–1824. 10.1002/acn3.50873 DOI: 10.1002/acn3.50873
Almdahl IS, Lauridsen C, Selnes P, Kalheim LF, Coello C, Gajdzik B et al (2017) Cerebrospinal fluid levels of amyloid beta 1–43 mirror 1–42 in relation to imaging biomarkers of Alzheimer’s disease. Front Aging Neurosci 9:9. 10.3389/fnagi.2017.00009 DOI: 10.3389/fnagi.2017.00009
Ashburner M, Ball CA, Blake JA, Botstein D, Butler H, Cherry JM et al (2000) Gene ontology: tool for the unification of biology. The Gene Ontology Consortium. Nat Genet 25:25–29. 10.1038/75556 DOI: 10.1038/75556
Bellenguez C, Küçükali F, Jansen IE, Kleineidam L, Moreno-Grau S, Amin N et al (2022) New insights into the genetic etiology of Alzheimer’s disease and related dementias. Nat Genet 54:412–436. 10.1038/s41588-022-01024-z DOI: 10.1038/s41588-022-01024-z
Benner C, Havulinna AS, Järvelin MR, Salomaa V, Ripatti S, Pirinen M (2017) Prospects of fine-mapping trait-associated genomic regions by using summary statistics from genome-wide association studies. Am J Hum Genet 101:539–551. 10.1016/j.ajhg.2017.08.012 DOI: 10.1016/j.ajhg.2017.08.012
Bettcher BM, Tansey MG, Dorothée G, Heneka MT (2021) Peripheral and central immune system crosstalk in Alzheimer disease—a research prospectus. Nat Rev Neurol 17:689–701. 10.1038/s41582-021-00549-x DOI: 10.1038/s41582-021-00549-x
Bulik-Sullivan BK, Loh P-R, Finucane HK, Ripke S, Yang J, Patterson N et al (2015) LD Score regression distinguishes confounding from polygenicity in genome-wide association studies. Nat Genet 47:291–295. 10.1038/ng.3211 DOI: 10.1038/ng.3211
Chang CC, Chow CC, Tellier LC, Vattikuti S, Purcell SM, Lee JJ (2015) Second-generation PLINK: rising to the challenge of larger and richer datasets. GigaScience. 10.1186/s13742-015-0047-8 DOI: 10.1186/s13742-015-0047-8
Chapuis J, Hansmannel F, Gistelinck M, Mounier A, Van Cauwenberghe C, Kolen KV et al (2013) Increased expression of BIN1 mediates Alzheimer genetic risk by modulating tau pathology. Mol Psychiatry 18:1225–1234. 10.1038/mp.2013.1 DOI: 10.1038/mp.2013.1
Cruchaga C, Kauwe JS, Harari O, Jin SC, Cai Y, Karch CM et al (2013) GWAS of cerebrospinal fluid tau levels identifies risk variants for Alzheimer’s disease. Neuron 78:256–268. 10.1016/j.neuron.2013.02.026 DOI: 10.1016/j.neuron.2013.02.026
Das S, Forer L, Schönherr S, Sidore C, Locke AE, Kwong A et al (2016) Next-generation genotype imputation service and methods. Nat Genet 48:1284–1287. 10.1038/ng.3656 DOI: 10.1038/ng.3656
de Leeuw CA, Mooij JM, Heskes T, Posthuma D (2015) MAGMA: generalized gene-set analysis of GWAS data. PLoS Comput Biol 11:e1004219. 10.1371/journal.pcbi.1004219 DOI: 10.1371/journal.pcbi.1004219
De Roeck A, Van Broeckhoven C, Sleegers K (2019) The role of ABCA7 in Alzheimer’s disease: evidence from genomics, transcriptomics and methylomics. Acta Neuropathol 138:201–220. 10.1007/s00401-019-01994-1 DOI: 10.1007/s00401-019-01994-1
de Rojas I, Moreno-Grau S, Tesi N, Grenier-Boley B, Andrade V, Jansen IE et al (2021) Common variants in Alzheimer’s disease and risk stratification by polygenic risk scores. Nat Commun 12:3417. 10.1038/s41467-021-22491-8 DOI: 10.1038/s41467-021-22491-8
Deming Y, Li Z, Kapoor M, Harari O, Del-Aguila JL, Black K et al (2017) Genome-wide association study identifies four novel loci associated with Alzheimer’s endophenotypes and disease modifiers. Acta Neuropathol 133:839–856. 10.1007/s00401-017-1685-y DOI: 10.1007/s00401-017-1685-y
El Khoury J, Toft M, Hickman SE, Means TK, Terada K, Geula C et al (2007) Ccr2 deficiency impairs microglial accumulation and accelerates progression of Alzheimer-like disease. Nat Med 13:432–438. 10.1038/nm1555 DOI: 10.1038/nm1555
Elsworth B, Lyon M, Alexander T, Liu Y, Matthews P, Hallett J et al (2020) The MRC IEU OpenGWAS data infrastructure. bioRxiv. 10.1101/2020.08.10.244293 DOI: 10.1101/2020.08.10.244293
Fitz NF, Nam KN, Wolfe CM, Letronne F, Playso BE, Iordanova BE et al (2021) Phospholipids of APOE lipoproteins activate microglia in an isoform-specific manner in preclinical models of Alzheimer’s disease. Nat Commun 12:3416. 10.1038/s41467-021-23762-0 DOI: 10.1038/s41467-021-23762-0
Fladby T, Pålhaugen L, Selnes P, Waterloo K, Bråthen G, Hessen E et al (2017) Detecting at-risk Alzheimer’s disease cases. J Alzheimers Dis 60:97–105. 10.3233/jad-170231 DOI: 10.3233/jad-170231
Franzmeier N, Rubinski A, Neitzel J, Ewers M, Weiner MW, Aisen P et al (2019) The BIN1 rs744373 SNP is associated with increased tau-PET levels and impaired memory. Nat Commun 10:1766. 10.1038/s41467-019-09564-5 DOI: 10.1038/s41467-019-09564-5
Geijselaers SLC, Aalten P, Ramakers I, De Deyn PP, Heijboer AC, Koek HL et al (2018) Association of cerebrospinal fluid (CSF) insulin with cognitive performance and CSF biomarkers of Alzheimer’s disease. J Alzheimers Dis 61:309–320. 10.3233/jad-170522 DOI: 10.3233/jad-170522
Giambartolomei C, Vukcevic D, Schadt EE, Franke L, Hingorani AD, Wallace C et al (2014) Bayesian test for colocalisation between pairs of genetic association studies using summary statistics. PLoS Genet 10:e1004383. 10.1371/journal.pgen.1004383 DOI: 10.1371/journal.pgen.1004383
Goate A, Chartier-Harlin MC, Mullan M, Brown J, Crawford F, Fidani L et al (1991) Segregation of a missense mutation in the amyloid precursor protein gene with familial Alzheimer’s disease. Nature 349:704–706. 10.1038/349704a0 DOI: 10.1038/349704a0
Gottesman II, Gould TD (2003) The endophenotype concept in psychiatry: etymology and strategic intentions. Am J Psychiatry 160:636–645. 10.1176/appi.ajp.160.4.636 DOI: 10.1176/appi.ajp.160.4.636
Grimmer T, Riemenschneider M, Förstl H, Henriksen G, Klunk WE, Mathis CA et al (2009) Beta amyloid in Alzheimer’s disease: increased deposition in brain is reflected in reduced concentration in cerebrospinal fluid. Biol Psychiatry 65:927–934. 10.1016/j.biopsych.2009.01.027 DOI: 10.1016/j.biopsych.2009.01.027
Hammond TR, Marsh SE, Stevens B (2019) Immune Signaling in Neurodegeneration. Immunity 50:955–974. 10.1016/j.immuni.2019.03.016 DOI: 10.1016/j.immuni.2019.03.016
Hardy JA, Higgins GA (1992) Alzheimer’s disease: the amyloid cascade hypothesis. Science (New York, NY) 256:184–185. 10.1126/science.1566067 DOI: 10.1126/science.1566067
He Z, Guo JL, McBride JD, Narasimhan S, Kim H, Changolkar L et al (2018) Amyloid-β plaques enhance Alzheimer’s brain tau-seeded pathologies by facilitating neuritic plaque tau aggregation. Nat Med 24:29–38. 10.1038/nm.4443 DOI: 10.1038/nm.4443
Hemani G, Zheng J, Elsworth B, Wade KH, Haberland V, Baird D et al (2018) The MR-Base platform supports systematic causal inference across the human phenome. Elife. 10.7554/eLife.34408 DOI: 10.7554/eLife.34408
Husain MA, Laurent B, Plourde M (2021) APOE and Alzheimer’s disease: from lipid transport to physiopathology and therapeutics. Front Neurosci. 10.3389/fnins.2021.630502 DOI: 10.3389/fnins.2021.630502
Jansen IE, Savage JE, Watanabe K, Bryois J, Williams DM, Steinberg S et al (2019) Genome-wide meta-analysis identifies new loci and functional pathways influencing Alzheimer’s disease risk. Nat Genet 51:404–413. 10.1038/s41588-018-0311-9 DOI: 10.1038/s41588-018-0311-9
Jessen F, Spottke A, Boecker H, Brosseron F, Buerger K, Catak C et al (2018) Design and first baseline data of the DZNE multicenter observational study on predementia Alzheimer’s disease (DELCODE). Alzheimer’s Res Ther 10:15. 10.1186/s13195-017-0314-2 DOI: 10.1186/s13195-017-0314-2
Johansson JU, Brubaker WD, Javitz H, Bergen AW, Nishita D, Trigunaite A et al (2018) Peripheral complement interactions with amyloid β peptide in Alzheimer’s disease: polymorphisms, structure, and function of complement receptor 1. Alzheimer’s Dementia 14:1438–1449. 10.1016/j.jalz.2018.04.003 DOI: 10.1016/j.jalz.2018.04.003
Kaipainen A, Jääskeläinen O, Liu Y, Haapalinna F, Nykänen N, Vanninen R et al (2020) Cerebrospinal fluid and MRI biomarkers in neurodegenerative diseases: a retrospective memory clinic-based study. J Alzheimers Dis 75:751–765. 10.3233/jad-200175 DOI: 10.3233/jad-200175
Karczewski KJ, Francioli LC, Tiao G, Cummings BB, Alföldi J, Wang Q et al (2020) The mutational constraint spectrum quantified from variation in 141,456 humans. Nature 581:434–443. 10.1038/s41586-020-2308-7 DOI: 10.1038/s41586-020-2308-7
Karran E, Mercken M, De Strooper B (2011) The amyloid cascade hypothesis for Alzheimer’s disease: an appraisal for the development of therapeutics. Nat Rev Drug Discov 10:698–712. 10.1038/nrd3505 DOI: 10.1038/nrd3505
Kerimov N, Hayhurst JD, Peikova K, Manning JR, Walter P, Kolberg L et al (2021) A compendium of uniformly processed human gene expression and splicing quantitative trait loci. Nat Genet 53:1290–1299. 10.1038/s41588-021-00924-w DOI: 10.1038/s41588-021-00924-w
Kloske CM, Wilcock DM (2020) The important interface between apolipoprotein E and neuroinflammation in Alzheimer’s disease. Front Immunol. 10.3389/fimmu.2020.00754 DOI: 10.3389/fimmu.2020.00754
Kolberg L, Raudvere U, Kuzmin I, Vilo J, Peterson H (2020) gprofiler2–an R package for gene list functional enrichment analysis and namespace conversion toolset g:Profiler. F1000Res. 10.12688/f1000research.24956.2 DOI: 10.12688/f1000research.24956.2
Kornhuber J, Schmidtke K, Frolich L, Perneczky R, Wolf S, Hampel H et al (2009) Early and differential diagnosis of dementia and mild cognitive impairment: design and cohort baseline characteristics of the German Dementia Competence Network. Dement Geriatr Cogn Disord 27:404–417. 10.1159/000210388 DOI: 10.1159/000210388
Kunkle BW, Grenier-Boley B, Sims R, Bis JC, Damotte V, Naj AC et al (2019) Genetic meta-analysis of diagnosed Alzheimer’s disease identifies new risk loci and implicates Aβ, tau, immunity and lipid processing. Nat Genet 51:414–430. 10.1038/s41588-019-0358-2 DOI: 10.1038/s41588-019-0358-2
Merico D, Isserlin R, Stueker O, Emili A, Bader GD (2010) Enrichment map: a network-based method for gene-set enrichment visualization and interpretation. PLoS ONE 5:e13984. 10.1371/journal.pone.0013984 DOI: 10.1371/journal.pone.0013984
Minami SS, Min S-W, Krabbe G, Wang C, Zhou Y, Asgarov R et al (2014) Progranulin protects against amyloid β deposition and toxicity in Alzheimer’s disease mouse models. Nat Med 20:1157–1164. 10.1038/nm.3672 DOI: 10.1038/nm.3672
Miyagawa T, Ebinuma I, Morohashi Y, Hori Y, Young Chang M, Hattori H et al (2016) BIN1 regulates BACE1 intracellular trafficking and amyloid-β production. Hum Mol Genet 25:2948–2958. 10.1093/hmg/ddw146 DOI: 10.1093/hmg/ddw146
Mulder C, Verwey NA, van der Flier WM, Bouwman FH, Kok A, van Elk EJ (2010) Amyloid-beta(1–42), total tau, and phosphorylated tau as cerebrospinal fluid biomarkers for the diagnosis of Alzheimer disease. Clin Chem 56:248–253. 10.1373/clinchem.2009.130518 DOI: 10.1373/clinchem.2009.130518
Najar J, van der Lee SJ, Joas E, Wetterberg H, Hardy J, Guerreiro R et al (2021) Polygenic risk scores for Alzheimer’s disease are related to dementia risk in APOE ɛ4 negatives. Alzheimer’s Dementia: Diagn Assess Dis Monitor 13:e12142. 10.1002/dad2.12142 DOI: 10.1002/dad2.12142
Olsson B, Lautner R, Andreasson U, Öhrfelt A, Portelius E, Bjerke M et al (2016) CSF and blood biomarkers for the diagnosis of Alzheimer’s disease: a systematic review and meta-analysis. Lancet Neurol 15:673–684. 10.1016/s1474-4422(16)00070-3 DOI: 10.1016/s1474-4422(16)00070-3
Ramirez A, van der Flier WM, Herold C, Ramonet D, Heilmann S, Lewczuk P et al (2014) SUCLG2 identified as both a determinator of CSF Aβ1-42 levels and an attenuator of cognitive decline in Alzheimer’s disease. Hum Mol Genet 23:6644–6658. 10.1093/hmg/ddu372 DOI: 10.1093/hmg/ddu372
Sartori M, Mendes T, Desai S, Lasorsa A, Herledan A, Malmanche N et al (2019) BIN1 recovers tauopathy-induced long-term memory deficits in mice and interacts with Tau through Thr(348) phosphorylation. Acta Neuropathol 138:631–652. 10.1007/s00401-019-02017-9 DOI: 10.1007/s00401-019-02017-9
Sherrington R, Froelich S, Sorbi S, Campion D, Chi H, Rogaeva EA et al (1996) Alzheimer’s disease associated with mutations in presenilin 2 is rare and variably penetrant. Hum Mol Genet 5:985–988. 10.1093/hmg/5.7.985 DOI: 10.1093/hmg/5.7.985
Sherrington R, Rogaev EI, Liang Y, Rogaeva EA, Levesque G, Ikeda M et al (1995) Cloning of a gene bearing missense mutations in early-onset familial Alzheimer’s disease. Nature 375:754–760. 10.1038/375754a0 DOI: 10.1038/375754a0
Shi Y, Holtzman DM (2018) Interplay between innate immunity and Alzheimer disease: APOE and TREM2 in the spotlight. Nat Rev Immunol 18:759–772. 10.1038/s41577-018-0051-1 DOI: 10.1038/s41577-018-0051-1
Shi Y, Yamada K, Liddelow SA, Smith ST, Zhao L, Luo W et al (2017) ApoE4 markedly exacerbates tau-mediated neurodegeneration in a mouse model of tauopathy. Nature 549:523–527. 10.1038/nature24016 DOI: 10.1038/nature24016
Sims R, van der Lee SJ, Naj AC, Bellenguez C, Badarinarayan N, Jakobsdottir J et al (2017) Rare coding variants in PLCG2, ABI3, and TREM2 implicate microglial-mediated innate immunity in Alzheimer’s disease. Nat Genet 49:1373–1384. 10.1038/ng.3916 DOI: 10.1038/ng.3916
Somers C, Struyfs H, Goossens J, Niemantsverdriet E, Luyckx J, De Roeck N et al (2016) A decade of cerebrospinal fluid biomarkers for Alzheimer’s disease in Belgium. J Alzheimers Dis 54:383–395. 10.3233/jad-151097 DOI: 10.3233/jad-151097
Sunderland T, Linker G, Mirza N, Putnam KT, Friedman DL, Kimmel LH et al (2003) Decreased beta-amyloid1-42 and increased tau levels in cerebrospinal fluid of patients with Alzheimer disease. JAMA 289:2094–2103. 10.1001/jama.289.16.2094 DOI: 10.1001/jama.289.16.2094
Taliun D, Harris D, Kessler M, Carlson J, Szpiech Z, Torres R et al (2019) Sequencing of 53,831 diverse genomes from the NHLBI TOPMed Program. bioRxiv. 10.1101/563866 DOI: 10.1101/563866
Therriault J, Benedet AL, Pascoal TA, Mathotaarachchi S, Chamoun M, Savard M et al (2020) Association of apolipoprotein E ε4 with medial temporal tau independent of amyloid-β. JAMA Neurol 77:470–479. 10.1001/jamaneurol.2019.4421 DOI: 10.1001/jamaneurol.2019.4421
Tijms BM, Gobom J, Reus L, Jansen I, Hong S, Dobricic V et al (2020) Pathophysiological subtypes of Alzheimer’s disease based on cerebrospinal fluid proteomics. Brain 143:3776–3792. 10.1093/brain/awaa325 DOI: 10.1093/brain/awaa325
Tijms BM, Willemse EAJ, Zwan MD, Mulder SD, Visser PJ, van Berckel BNM et al (2018) Unbiased approach to counteract upward drift in cerebrospinal fluid amyloid-β 1–42 analysis results. Clin Chem 64:576–585. 10.1373/clinchem.2017.281055 DOI: 10.1373/clinchem.2017.281055
Uddin MS, Kabir MT, Begum MM, Islam MS, Behl T, Ashraf GM (2021) Exploring the role of CLU in the pathogenesis of Alzheimer’s disease. Neurotox Res 39:2108–2119. 10.1007/s12640-020-00271-4 DOI: 10.1007/s12640-020-00271-4
van der Kant R, Goldstein LSB, Ossenkoppele R (2020) Amyloid-β-independent regulators of tau pathology in Alzheimer disease. Nat Rev Neurosci 21:21–35. 10.1038/s41583-019-0240-3 DOI: 10.1038/s41583-019-0240-3
Vojinovic D, Adams HH, Jian X, Yang Q, Smith AV, Bis JC et al (2018) Genome-wide association study of 23,500 individuals identifies 7 loci associated with brain ventricular volume. Nat Commun 9:3945. 10.1038/s41467-018-06234-w DOI: 10.1038/s41467-018-06234-w
Voskobiynyk Y, Roth JR, Cochran JN, Rush T, Carullo NV, Mesina JS et al (2020) Alzheimer’s disease risk gene BIN1 induces Tau-dependent network hyperexcitability. Elife. 10.7554/eLife.57354 DOI: 10.7554/eLife.57354
Wallace C (2020) Eliciting priors and relaxing the single causal variant assumption in colocalisation analyses. PLoS Genet 16:e1008720. 10.1371/journal.pgen.1008720 DOI: 10.1371/journal.pgen.1008720
Wang C, Najm R, Xu Q, Jeong DE, Walker D, Balestra ME et al (2018) Gain of toxic apolipoprotein E4 effects in human iPSC-derived neurons is ameliorated by a small-molecule structure corrector. Nat Med 24:647–657. 10.1038/s41591-018-0004-z DOI: 10.1038/s41591-018-0004-z
Watanabe K, Taskesen E, van Bochoven A, Posthuma D (2017) Functional mapping and annotation of genetic associations with FUMA. Nat Commun 8:1826. 10.1038/s41467-017-01261-5 DOI: 10.1038/s41467-017-01261-5
Wightman DP, Jansen IE, Savage JE, Shadrin AA, Bahrami S, Rongve A et al (2020) Largest GWAS (N=1,126,563) of Alzheimer’s disease implicates microglia and immune cells. medRxiv. 10.1101/2020.11.20.20235275 DOI: 10.1101/2020.11.20.20235275
Willer CJ, Li Y, Abecasis GR (2010) METAL: fast and efficient meta-analysis of genomewide association scans. Bioinformatics (Oxford, England) 26:2190–2191. 10.1093/bioinformatics/btq340 DOI: 10.1093/bioinformatics/btq340
Wyss-Coray T, Yan F, Lin AH, Lambris JD, Alexander JJ, Quigg RJ et al (2002) Prominent neurodegeneration and increased plaque formation in complement-inhibited Alzheimer’s mice. Proc Natl Acad Sci USA 99:10837–10842. 10.1073/pnas.162350199 DOI: 10.1073/pnas.162350199
Yang C, Farias FHG, Ibanez L, Suhy A, Sadler B, Fernandez MV et al (2021) Genomic atlas of the proteome from brain, CSF and plasma prioritizes proteins implicated in neurological disorders. Nat Neurosci 24:1302–1312. 10.1038/s41593-021-00886-6 DOI: 10.1038/s41593-021-00886-6
Yang J, Lee SH, Goddard ME, Visscher PM (2011) GCTA: a tool for genome-wide complex trait analysis. Am J Hum Genet 88:76–82. 10.1016/j.ajhg.2010.11.011 DOI: 10.1016/j.ajhg.2010.11.011
Yeh FL, Wang Y, Tom I, Gonzalez LC, Sheng M (2016) TREM2 binds to apolipoproteins, including APOE and CLU/APOJ, and thereby facilitates uptake of amyloid-beta by microglia. Neuron 91:328–340. 10.1016/j.neuron.2016.06.015 DOI: 10.1016/j.neuron.2016.06.015
Yiannopoulou KG, Anastasiou AI, Zachariou V, Pelidou SH (2019) Reasons for failed trials of disease-modifying treatments for Alzheimer disease and their contribution in recent research. Biomedicines. 10.3390/biomedicines7040097 DOI: 10.3390/biomedicines7040097
Young AMH, Kumasaka N, Calvert F, Hammond TR, Knights A, Panousis N et al (2021) A map of transcriptional heterogeneity and regulatory variation in human microglia. Nat Genet 53:861–868. 10.1038/s41588-021-00875-2 DOI: 10.1038/s41588-021-00875-2
Zettergren A, Höglund K, Kern S, Thorvaldsson V, Johan Skoog M, Hansson O et al (2019) Association of IL1RAP-related genetic variation with cerebrospinal fluid concentration of Alzheimer-associated tau protein. Sci Rep 9:2460. 10.1038/s41598-018-36650-3 DOI: 10.1038/s41598-018-36650-3
Zhao Z, Sagare AP, Ma Q, Halliday MR, Kong P, Kisler K et al (2015) Central role for PICALM in amyloid-β blood-brain barrier transcytosis and clearance. Nat Neurosci 18:978–987. 10.1038/nn.4025 DOI: 10.1038/nn.4025
Zheng J, Erzurumluoglu AM, Elsworth BL, Kemp JP, Howe L, Haycock PC et al (2017) LD Hub: a centralized database and web interface to perform LD score regression that maximizes the potential of summary level GWAS data for SNP heritability and genetic correlation analysis. Bioinformatics (Oxford, England) 33:272–279. 10.1093/bioinformatics/btw613 DOI: 10.1093/bioinformatics/btw613
Zhu X-C, Yu J-T, Jiang T, Wang P, Cao L, Tan L (2015) CR1 in Alzheimer’s disease. Mol Neurobiol 51:753–765. 10.1007/s12035-014-8723-8 DOI: 10.1007/s12035-014-8723-8
