SynthesisNature communications2026
GWAS meta-analysis of cerebrospinal fluid Alzheimer's biomarkers reveals loci regulating lipids, brain volume and autophagy.
Abstract readMeta-Analysis
In one paragraph
Synthesis in Nature communications, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
1 citing paper in PubMed.
- Genetic evidence suggests a protective role of immunoglobulin M in Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
Corrections and comments
- Update of
Authors and funding
155 authors.
Jigyasha Timsina *Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA.ORCID http://orcid.org/0000-0003-4794-9187
Chenyang Jiang *Alzheimer Center Amsterdam, Neurology, Vrije Universiteit Amsterdam, Amsterdam UMC Location VUmc, Amsterdam, The Netherlands.
Daniel L McCartneyCentre for Genomic and Experimental Medicine, Institute of Genetics and Cancer, The University of Edinburgh, Edinburgh, UK.
Feifei TaoHuman Genetics and Causal Biology, Eisai Center for Genetics-Guided Dementia Discovery, Eisai Inc, Cambridge, MA, USA.
Maria Carolina DalmassoDivision of Neurogenetics and Molecular Psychiatry, Department of Psychiatry and Psychotherapy, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany.ORCID http://orcid.org/0000-0002-4901-9955
Jenna NajarAlzheimer Center Amsterdam, Neurology, Vrije Universiteit Amsterdam, Amsterdam UMC Location VUmc, Amsterdam, The Netherlands.ORCID http://orcid.org/0000-0002-1762-4413
Federica AnastasiBarcelonaβeta Brain Research Center (BBRC), Pasqual Maragall Foundation, Barcelona, Spain.ORCID http://orcid.org/0000-0002-9304-5421
Olena OhleiLübeck Interdisciplinary Platform for Genome Analytics, University of Lübeck, Lübeck, Germany.
Raquel Puerta FuentesAce Alzheimer Center Barcelona, Universitat Internacional de Catalunya, Barcelona, Spain.ORCID http://orcid.org/0000-0002-1191-5893
Chenyu YangNeuroGenomics and Informatics Center, Washington University School of Medicine, St. Louis, MO, USA.
Joseph BradleyDepartment of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA.ORCID http://orcid.org/0000-0003-0217-4808
Daniel WesternDepartment of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA.ORCID http://orcid.org/0000-0003-3725-9553
Muhammad AliDepartment of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA.ORCID http://orcid.org/0000-0002-1399-6631
Ciyang WangDepartment of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA.ORCID http://orcid.org/0000-0001-5253-0490
Chengran YangDepartment of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA.ORCID http://orcid.org/0000-0003-4577-5590
Ying WuHuman Genetics and Causal Biology, Eisai Center for Genetics-Guided Dementia Discovery, Eisai Inc, Cambridge, MA, USA.
Menghan LiuDepartment of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA.ORCID http://orcid.org/0009-0008-9902-5983
John BuddeDepartment of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA.ORCID http://orcid.org/0000-0001-7778-7276
Julie WilliamsUK Dementia Research Institute at Cardiff, Cardiff, UK.ORCID http://orcid.org/0000-0002-4069-0259
Rebecca MahoneyUK Dementia Research Institute at Cardiff, Cardiff, UK.
Atahualpa Castillo MoralesUK Dementia Research Institute at Cardiff, Cardiff, UK.
Timothy J HohmanVanderbilt Memory and Alzheimer's Center, Vanderbilt University Medical Center, Nashville, TN, USA.ORCID http://orcid.org/0000-0002-3377-7014
Logan DumitrescuVanderbilt Memory and Alzheimer's Center, Vanderbilt University Medical Center, Nashville, TN, USA.ORCID http://orcid.org/0000-0002-9782-9944
Ting-Chen WangVanderbilt Memory and Alzheimer's Center, Vanderbilt University Medical Center, Nashville, TN, USA.
Niccolo' TesiAlzheimer Center Amsterdam, Neurology, Vrije Universiteit Amsterdam, Amsterdam UMC Location VUmc, Amsterdam, The Netherlands.ORCID http://orcid.org/0000-0002-1413-5091
Silke KernNeuropsychiatric 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.
Margda WaernNeuropsychiatric 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.ORCID http://orcid.org/0000-0002-8330-6915
Ingmar SkoogNeuropsychiatric 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.
Argonde van HartenAlzheimer Center Amsterdam, Neurology, Vrije Universiteit Amsterdam, Amsterdam UMC Location VUmc, Amsterdam, The Netherlands.
Yolande A L PijnenburgAlzheimer Center Amsterdam, Neurology, Vrije Universiteit Amsterdam, Amsterdam UMC Location VUmc, Amsterdam, The Netherlands.
Wiesje M van der FlierAlzheimer Center Amsterdam, Neurology, Vrije Universiteit Amsterdam, Amsterdam UMC Location VUmc, Amsterdam, The Netherlands.ORCID http://orcid.org/0000-0001-8766-6224
Pascual Sánchez-JuanReina Sofia Alzheimer Center, CIEN Foundation, ISCIII, Madrid, Spain.
Eloy Rodriguez-RodriguezCentro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED), Instituto de Salud Carlos III, Madrid, Spain.ORCID http://orcid.org/0000-0001-7742-677X
Luca KleineidamDepartment of Cognitive Disorders and Old Age Psychiatry, University Hospital Bonn, Bonn, Germany.ORCID http://orcid.org/0009-0006-3309-6856
Oliver PetersGerman Center for Neurodegenerative Diseases (DZNE), Berlin, Germany.ORCID http://orcid.org/0000-0003-0568-2998
Anja SchneiderDepartment of Cognitive Disorders and Old Age Psychiatry, University Hospital Bonn, Bonn, Germany.
Fahri KüçükaliDepartment of Biomedical Sciences, University of Antwerp, Antwerp, Belgium.ORCID http://orcid.org/0000-0002-3835-9639
Céline BellenguezUniv. Lille, Inserm, CHU Lille, Institut Pasteur de Lille, LabEx DISTALZ-U1167-RID-AGE Facteurs de Risque et Determiants moléculaires des maladies liées au vieillissement, Lille, France.ORCID http://orcid.org/0000-0002-1240-7874
Benjamin Grenier-BoleyUniv. Lille, Inserm, CHU Lille, Institut Pasteur de Lille, LabEx DISTALZ-U1167-RID-AGE Facteurs de Risque et Determiants moléculaires des maladies liées au vieillissement, Lille, France.
Sami HeikkinenInstitute of Biomedicine, University of Eastern Finland, Kuopio, Finland.ORCID http://orcid.org/0000-0002-6083-2402
Itziar de RojasAce Alzheimer Center Barcelona, Universitat Internacional de Catalunya, Barcelona, Spain.ORCID http://orcid.org/0000-0002-2148-381X
Dan RujescuMartin-Luther-University Halle-Wittenberg, University Clinic and Outpatient Clinic for Psychiatry, Psychotherapy and Psychosomatics, Halle (Saale), Germany.ORCID http://orcid.org/0000-0002-1432-313X
Norbert ScherbaumLVR-University Hospital Essen, Department of Psychiatry and Psychotherapy, Medical Faculty, University of Duisburg-Essen, Essen, Germany.ORCID http://orcid.org/0000-0003-1759-6990
Lucrezia HausnerDepartment of Geriatric Psychiatry, Central Institute for Mental Health Mannheim, Faculty Mannheim, University of Heidelberg, Heidelberg, Germany.ORCID http://orcid.org/0000-0001-9009-2356
Emrah DüzelGerman Center for Neurodegenerative Diseases (DZNE), Magdeburg, Germany.
Timo GrimmerCenter for Cognitive Disorders, Department of Psychiatry and Psychotherapy, Technical University of Munich, TUM School of Medicine and Health, Munich, Germany.
Jens WiltfangDepartment of Psychiatry and Psychotherapy, University Medical Center Goettingen, Goettingen, Germany.ORCID http://orcid.org/0000-0003-1492-5330
Rik VandenbergheDepartment of Neurology, UZ Leuven, Leuven, Belgium.
Sebastiaan EngelborghsDepartment of Biomedical Sciences, University of Antwerp, Antwerp, Belgium.ORCID http://orcid.org/0000-0003-0304-9785
Stefanie Heilmann-HeimbachInstitute of Human Genetics, University of Bonn, School of Medicine & University Hospital Bonn, Bonn, Germany.ORCID http://orcid.org/0000-0003-1057-465X
Matthias SchmidGerman Center for Neurodegenerative Diseases (DZNE), Bonn, Germany.
Thomas Tegos1st Department of Neurology, Medical school, Aristotle University of Thessaloniki, Thessaloniki, Greece.
Nikolaos Scarmeas1st Department of Neurology, Aiginition Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece.
Oriol Dols-IcardoCentro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED), Instituto de Salud Carlos III, Madrid, Spain.ORCID http://orcid.org/0000-0003-2656-8748
Fermin MorenoCentro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED), Instituto de Salud Carlos III, Madrid, Spain.ORCID http://orcid.org/0000-0001-5200-3164
Jordi Pérez-TurCentro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED), Instituto de Salud Carlos III, Madrid, Spain.ORCID http://orcid.org/0000-0002-9111-1712
María J BullidoCentro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED), Instituto de Salud Carlos III, Madrid, Spain.ORCID http://orcid.org/0000-0002-6477-1117
Raquel Sánchez-ValleAlzheimer's disease and other cognitive disorders unit. Service of Neurology. Hospital Clínic of Barcelona. Institut d'Investigacions Biomèdiques August Pi i Sunyer, University of Barcelona, Barcelona, Spain.
Victoria ÁlvarezLaboratorio de Genética. Hospital Universitario Central de Asturias, Oviedo, Spain.ORCID http://orcid.org/0000-0002-1916-2523
Pablo García-GonzálezAce Alzheimer Center Barcelona, Universitat Internacional de Catalunya, Barcelona, Spain.ORCID http://orcid.org/0000-0003-0125-5403
Pablo MirCentro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED), Instituto de Salud Carlos III, Madrid, Spain.ORCID http://orcid.org/0000-0003-1656-302X
Luis M RealUnidad Clínica de Enfermedades Infecciosas y Microbiología. Hospital Universitario de Valme, Sevilla, Spain.ORCID http://orcid.org/0000-0003-4932-7429
Gerard Piñol-RipollUnitat Trastorns Cognitius, Hospital Universitari Santa Maria de Lleida, Lleida, Spain.
Jose María García-AlbercaCentro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED), Instituto de Salud Carlos III, Madrid, Spain.ORCID http://orcid.org/0000-0003-2951-6644
Harro SeelaarAmsterdam Neuroscience, Neurodegeneration, Amsterdam, The Netherlands.ORCID http://orcid.org/0000-0003-1989-7527
Inez RamakersMaastricht University, Department of Psychiatry & Neuropsychologie, Alzheimer Center Limburg, Maastricht, the Netherlands.
Janne PapmaNeurology department Erasmus MC University Medical Center, Rotterdam, The Netherlands.
Marc HulsmanAlzheimer Center Amsterdam, Neurology, Vrije Universiteit Amsterdam, Amsterdam UMC Location VUmc, Amsterdam, The Netherlands.ORCID http://orcid.org/0000-0002-9889-3606
Christoph LaskeGerman Center for Neurodegenerative Diseases (DZNE), Tübingen, Germany.
Stefan TeipelGerman Center for Neurodegenerative Diseases (DZNE), Rostock, Germany.
Josef PrillerGerman Center for Neurodegenerative Diseases (DZNE), Berlin, Germany.ORCID http://orcid.org/0000-0001-7596-0979
Robert PerneczkyGerman Center for Neurodegenerative Diseases (DZNE Munich), Munich, Germany.ORCID http://orcid.org/0000-0003-1981-7435
Katharina BuergerGerman Center for Neurodegenerative Diseases (DZNE Munich), Munich, Germany.
Markus M NöthenInstitute of Human Genetics; University of Bonn, School of Medicine & University Hospital Bonn, Bonn, Germany.ORCID http://orcid.org/0000-0002-8770-2464
Piotr LewczukDepartment of Psychiatry and Psychotherapy, Universitätsklinikum Erlangen, and Friedrich-Alexander Universität Erlangen-Nürnberg, Erlangen, Germany.ORCID http://orcid.org/0000-0002-8101-6535
Johannes KornhuberDepartment of Psychiatry and Psychotherapy, Universitätsklinikum Erlangen, and Friedrich-Alexander Universität Erlangen-Nürnberg, Erlangen, Germany.ORCID http://orcid.org/0000-0002-8096-3987
Harald HampelSorbonne University, Alzheimer Precision Medicine (APM), AP-HP, Pitié-Salpêtrière Hospital, Boulevard de l'hôpital, Paris, France.
Ina GieglingDivision of General Psychiatry, Dept. of Psychiatry and Psychotherapy, Medical University of Vienna, Vienna, Austria.ORCID http://orcid.org/0000-0001-8407-7512
Oliver GoldhardtDepartment of Psychiatry and Psychotherapy, University Medical Center Goettingen, Goettingen, Germany.ORCID http://orcid.org/0000-0002-3841-3391
Janine Diehl-SchmidDepartment of Psychiatry and Psychotherapy, University Medical Center Goettingen, Goettingen, Germany.
Victor AndradeDivision of Neurogenetics and Molecular Psychiatry, Department of Psychiatry and Psychotherapy, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany.
Michael Mt HenekaDivision of Neurogenetics and Molecular Psychiatry, Department of Psychiatry and Psychotherapy, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany.
Lutz FrölichDepartment of Geriatric Psychiatry, Central Institute for Mental Health Mannheim, Faculty Mannheim, University of Heidelberg, Heidelberg, Germany.ORCID http://orcid.org/0000-0003-1494-0813
Jonathan VogelgsangDepartment of Psychiatry and Psychotherapy, University Medical Center Goettingen, Goettingen, Germany.ORCID http://orcid.org/0000-0001-9326-8193
Caroline GraffDivision of Neurogeriatrics, Department NVS, Karolinska Institutet, Center for Alzheimer Research, Stockholm, Sweden.ORCID http://orcid.org/0000-0002-9949-2951
Hakan ThonbergDivision of Neurogeriatrics, Department NVS, Karolinska Institutet, Center for Alzheimer Research, Stockholm, Sweden.
Abbe UllgrenDivision of Neurogeriatrics, Department NVS, Karolinska Institutet, Center for Alzheimer Research, Stockholm, Sweden.
Goran PapenbergAging Research Center, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet and Stockholm University, Stockholm, Sweden.
Jean-François DeleuzeUniversité Paris-Saclay, CEA, Centre National de Recherche en Génomique Humaine, Evry, France.ORCID http://orcid.org/0000-0002-5358-4463
Carole DufouilInserm, Bordeaux Population Health Research Center, UMR 1219, Univ. Bordeaux, ISPED, CIC 1401-EC, Univ Bordeaux, Bordeaux, France.ORCID http://orcid.org/0000-0003-2442-4476
Michael WagnerDepartment of Cognitive Disorders and Old Age Psychiatry, University Hospital Bonn, Bonn, Germany.ORCID http://orcid.org/0000-0003-2589-6440
Frank JessenGerman Center for Neurodegenerative Diseases (DZNE), Bonn, Germany.
Henne HolstegeAlzheimer Center Amsterdam, Neurology, Vrije Universiteit Amsterdam, Amsterdam UMC Location VUmc, Amsterdam, The Netherlands.ORCID http://orcid.org/0000-0002-7688-3087
Cornelia van DuijnDepartment of Epidemiology, ErasmusMC, Rotterdam, The Netherlands.ORCID http://orcid.org/0000-0002-2374-9204
Thibaud LebouvierUniv.Lille, Inserm, CHULille, Lille Neuroscience & Cognition, UMR-S1172, Lille, France.
Olivier HannonUniversité de Paris, EA 4468, APHP, Hôpital Broca, Paris, France.
Ville LeinonenDepartment of Neurosurgery, Kuopio University Hospital and Institute of Clinical Medicine-Neurosurgery, University of Eastern Finland, Kuopio, Finland.ORCID http://orcid.org/0000-0002-4282-4687
Hilkka SoininenDepartment of Neurology, Institute of Clinical Medicine, University of Eastern Finland, Kuopio, Finland.ORCID http://orcid.org/0000-0002-2785-9937
Sanna-Kaisa HerukkaDepartment of Neurology, Institute of Clinical Medicine, University of Eastern Finland, Kuopio, Finland.
Vilmantas GiedraitisDepartment of Public Health and Caring Sciences/Clinical Geriatrics, Uppsala University, Uppsala, Sweden.
Malin LöwenmarkDepartment of Public Health and Caring Sciences/Clinical Geriatrics, Uppsala University, Uppsala, Sweden.
Lena KilanderDepartment of Public Health and Caring Sciences/Clinical Geriatrics, Uppsala University, Uppsala, Sweden.
Patricia GeniusBarcelonaβeta Brain Research Center (BBRC), Pasqual Maragall Foundation, Barcelona, Spain.
Blanca RodríguezBarcelonaβeta Brain Research Center (BBRC), Pasqual Maragall Foundation, Barcelona, Spain.
Emma S LuckettDepartment of Radiology and Nuclear Medicine, Amsterdam UMC location VUmc, Amsterdam, Netherlands.
Arcadi NavarroBarcelonaβeta Brain Research Center (BBRC), Pasqual Maragall Foundation, Barcelona, Spain.
Amanda CanoAce Alzheimer Center Barcelona, Universitat Internacional de Catalunya, Barcelona, Spain.
Marta MarquiéAce Alzheimer Center Barcelona, Universitat Internacional de Catalunya, Barcelona, Spain.
Kaj BlennowClinical neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden.ORCID http://orcid.org/0000-0002-1890-4193
Henrik ZetterbergClinical neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden.ORCID http://orcid.org/0000-0003-3930-4354
Alberto LleoCentro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED), Instituto de Salud Carlos III, Madrid, Spain.ORCID http://orcid.org/0000-0002-2568-5478
Mercè BoadaAce Alzheimer Center Barcelona, Universitat Internacional de Catalunya, Barcelona, Spain.ORCID http://orcid.org/0000-0003-2617-3009
Agustin RuizAce Alzheimer Center Barcelona, Universitat Internacional de Catalunya, Barcelona, Spain.ORCID http://orcid.org/0000-0003-2633-2495
Virginia Man-Yee LeeDepartment of Pathology and Laboratory Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.ORCID http://orcid.org/0000-0003-3536-6902
Vivianna M Van DeerlinDepartment of Pathology and Laboratory Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.ORCID http://orcid.org/0000-0002-7400-9097
Yuetiva DemingWisconsin Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, USA.
Sterling C JohnsonDepartment of Medicine, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, USA.ORCID http://orcid.org/0000-0002-8501-545X
Corinne D EngelmanDepartment of Population Health Sciences, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, USA.
Pau PastorUnit of Neurodegenerative diseases, Department of Neurology, University Hospital Germans Trias i Pujol and The Germans Trias i Pujol Research Institute (IGTP) Badalona, Barcelona, Spain.ORCID http://orcid.org/0000-0002-7493-8777
Ignacio AlvarezUnit of Neurodegenerative diseases, Department of Neurology, University Hospital Germans Trias i Pujol and The Germans Trias i Pujol Research Institute (IGTP) Badalona, Barcelona, Spain.ORCID http://orcid.org/0000-0002-8537-3935
Elaine R PeskindVeterans Affairs Northwest Mental Illness Research, Education, and Clinical Center, Seattle, WA, USA.
Amanda J HeslegraveUK Dementia Research Institute at UCL, London, UK.
Andrew J SaykinIndiana Alzheimer's Disease Research Center, Department of Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, Indiana, USA.ORCID http://orcid.org/0000-0002-1376-8532
Kwangsik NhoIndiana Alzheimer's Disease Research Center, Department of Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, Indiana, USA.
Suzanne E SchindlerDepartment of Neurology, Washington University School of Medicine, St. Louis, MO, USA.ORCID http://orcid.org/0000-0002-1680-1465
John C MorrisDepartment of Neurology, Washington University School of Medicine, St. Louis, MO, USA.
David M HoltzmanDepartment of Neurology, Washington University School of Medicine, St. Louis, MO, USA.ORCID http://orcid.org/0000-0002-3400-0856
Eric McDadeDepartment of Neurology, Washington University School of Medicine, St. Louis, MO, USA.ORCID http://orcid.org/0000-0002-6764-3866
Alan E RentonRonald M. Loeb Center for Alzheimer's Disease, Icahn School of Medicine at Mount Sinai, New York, NY, USA.ORCID http://orcid.org/0000-0001-6702-8268
Alison GoateRonald M. Loeb Center for Alzheimer's Disease, Icahn School of Medicine at Mount Sinai, New York, NY, USA.ORCID http://orcid.org/0000-0002-0576-2472
Laura IbanezDepartment of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA.
Matthias RiemenschneiderDepartment of Psychiatry, Saarland University, Homburg, Germany.
Marilyn S AlbertDepartment of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Simon M LawsCentre for Precision Health, School of Medical Health Sciences, Edith Cowan University, Joondalup, WA, Australia.ORCID http://orcid.org/0000-0002-4355-7082
Tenielle PorterCentre for Precision Health, School of Medical Health Sciences, Edith Cowan University, Joondalup, WA, Australia.ORCID http://orcid.org/0000-0002-7887-6622
Eleanor K O'BrienCentre for Precision Health, School of Medical Health Sciences, Edith Cowan University, Joondalup, WA, Australia.ORCID http://orcid.org/0000-0001-5145-7340
Leslie M ShawGlenn Biggs Institute for Alzheimer's & Neurodegenerative Diseases and Department of Microbiology, Immunology and Molecular Genetics, Long School of Medicine, University of Texas Health Science Center, San Antonio, TX, USA.
Betty M TijmsAlzheimer Center Amsterdam, Neurology, Vrije Universiteit Amsterdam, Amsterdam UMC Location VUmc, Amsterdam, The Netherlands.ORCID http://orcid.org/0000-0002-2612-1797
Martin IngelssonKrembil Brain Institute, University Health Network, Toronto, ON, Canada.ORCID http://orcid.org/0000-0001-5466-8370
Pieter Jelle VisserDepartment of Neurology, Alzheimer Center Amsterdam, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam UMC, VUmc, Amsterdam, the Netherlands.ORCID http://orcid.org/0000-0001-8008-9727
Mikko HiltunenInstitute of Biomedicine, University of Eastern Finland, Kuopio, Finland.ORCID http://orcid.org/0000-0003-3566-4096
Kristel SleegersDepartment of Biomedical Sciences, University of Antwerp, Antwerp, Belgium.
Craig W RitchieScottish Brain Sciences, Scottish Gas Murrayfield Stadium, Edinburgh, UK.
Rebecca SimsDivision of Psychological Medicine and Clinical Neuroscience, School of Medicine, Cardiff University, Cardiff, UK.ORCID http://orcid.org/0000-0002-3885-1199
Michael BelloyNeuroGenomics and Informatics Center, Washington University School of Medicine, St. Louis, MO, USA.ORCID http://orcid.org/0000-0001-7748-9033
Jean-Charles LambertUniv. Lille, Inserm, CHU Lille, Institut Pasteur de Lille, LabEx DISTALZ-U1167-RID-AGE Facteurs de Risque et Determiants moléculaires des maladies liées au vieillissement, Lille, France.ORCID http://orcid.org/0000-0003-0829-7817
Natalia Vilor-TejedorBarcelonaβeta Brain Research Center (BBRC), Pasqual Maragall Foundation, Barcelona, Spain.ORCID http://orcid.org/0000-0003-4935-6721
Maria Victoria FernándezAce Alzheimer Center Barcelona, Universitat Internacional de Catalunya, Barcelona, Spain.
Qingqin S LiNeuroscience, Janssen Research & Development LLC, Titusville, NJ, USA.ORCID http://orcid.org/0000-0003-4182-4535
Michael W NagleHuman Genetics and Causal Biology, Eisai Center for Genetics-Guided Dementia Discovery, Eisai Inc, Cambridge, MA, USA.ORCID http://orcid.org/0000-0002-4677-7582
Riccardo E MarioniCentre for Genomic and Experimental Medicine, Institute of Genetics and Cancer, The University of Edinburgh, Edinburgh, UK.ORCID http://orcid.org/0000-0003-4430-4260
Alfredo RamirezDivision of Neurogenetics and Molecular Psychiatry, Department of Psychiatry and Psychotherapy, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany.ORCID http://orcid.org/0000-0003-4991-763X
Lars BertramLübeck Interdisciplinary Platform for Genome Analytics, University of Lübeck, Lübeck, Germany.ORCID http://orcid.org/0000-0002-0108-124X
Sven J van der LeeAlzheimer Center Amsterdam, Neurology, Vrije Universiteit Amsterdam, Amsterdam UMC Location VUmc, Amsterdam, The Netherlands.ORCID http://orcid.org/0000-0003-1606-8643
Carlos CruchagaDepartment of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA. cruchagac@wustl.edu.ORCID http://orcid.org/0000-0002-0276-2899
Funding
Project 1U19AG024904 · NIA · NORTHERN CALIFORNIA INSTITUTE/RES/EDU · PI RICHARD Justin PERRIN · 2016 to 2026
$226.7MAlzheimer's Disease Neuroimaging Initiative - SupplementU01AG024904 · NIA · NORTHERN CALIFORNIA INSTITUTE RES &EDUC · PI WEINER, MICHAEL W · 2004 to 2015
$121.0MTranslational pharmacoepidemiology: neuroprotection and neurotoxicity of antihypertensives and strong anticholinergicsU19AG066567 · NIA · KAISER FOUNDATION RESEARCH INSTITUTE · PI Paul K Crane, Andrea Z. LaCroix · 2021 to 2026
$80.4MSmartphone-Based "Burst" Cognitive AssessmentsP01AG003991 · NIA · WASHINGTON UNIVERSITY · PI JOHN MORRIS, Suzanne Elizabeth Schindler · 1985 to 2026
$69.5MImaging CoreU19AG032438 · NIA · WASHINGTON UNIVERSITY · PI BATEMAN, RANDALL J · 2010 to 2025
$53.9MThe natural history of AB accumulation in preclinical ADP01AG026276 · NIA · WASHINGTON UNIVERSITY · PI MORRIS, JOHN · 2005 to 2025
$49.5MSUPPLEMENT TO RUSH ALZHEIMERS DISEASE CENTER COREP30AG010161 · NIA · RUSH UNIVERSITY MEDICAL CENTER · PI BARNES, LISA L · 1991 to 2020
$49.1MNational Alzheimer's Coordinating CenterU24AG072122 · NIA · UNIVERSITY OF WASHINGTON · PI STEPHENS, KARI A · 2021 to 2025
$45.8MEPIDEMIOLOGY OF NEURAL RESERVE AND NEUROBIOLOGY IN AGINGR01AG017917 · NIA · RUSH UNIVERSITY MEDICAL CENTER · PI BENNETT, DAVID ALAN · 2001 to 2023
$43.3MTHE NIA GENETICS OF ALZHEIMER'S DISEASE DATA STORAGE SITEU24AG041689 · NIA · UNIVERSITY OF PENNSYLVANIA · PI LI-SAN WANG · 2012 to 2026
$42.3MPeripheral and Central Biomarkers of Alzheimer's Disease in Diverse CohortsU19AG074879 · NIA · MAYO CLINIC JACKSONVILLE · PI Mariet Allen · 2023 to 2026
$42.0MFurthering scientific understanding of mechanisms underlying resilience to the effects of AD pathology by incorporating state of the art quantification of gliosis, inflammation, & synaptic toxicityU01AG006781 · NIA · UNIVERSITY OF WASHINGTON · PI CRANE, PAUL K, LARSON, ERIC B · 1986 to 2020
$39.3MAlzheimer's Association ZEN-22-848604NIA NIH HHS P01 AG003991NIA NIH HHS P01 AG026276NIA NIH HHS P20 AG068024NIA NIH HHS P20 AG068053NIA NIH HHS P20 AG068077NIA NIH HHS P20 AG068082NIA NIH HHS P30 AG010161NIA NIH HHS P30 AG062421NIA NIH HHS P30 AG062422NIA NIH HHS P30 AG062429NIA NIH HHS P30 AG062677NIA NIH HHS P30 AG062715NIA NIH HHS P30 AG066444NIA NIH HHS P30 AG066462NIA NIH HHS P30 AG066468NIA NIH HHS P30 AG066506NIA NIH HHS P30 AG066507NIA NIH HHS P30 AG066508NIA NIH HHS P30 AG066509NIA NIH HHS P30 AG066511NIA NIH HHS P30 AG066512NIA NIH HHS P30 AG066514NIA NIH HHS P30 AG066515NIA NIH HHS P30 AG066518NIA NIH HHS P30 AG066519NIA NIH HHS P30 AG066530NIA NIH HHS P30 AG066546NIA NIH HHS P30 AG072931NIA NIH HHS P30 AG072946NIA NIH HHS P30 AG072947NIA NIH HHS P30 AG072958NIA NIH HHS P30 AG072959NIA NIH HHS P30 AG072972NIA NIH HHS P30 AG072973NIA NIH HHS P30 AG072975NIA NIH HHS P30 AG072976NIA NIH HHS P30 AG072977NIA NIH HHS P30 AG072978NIA NIH HHS P30 AG072979NIA NIH HHS R00 AG075238NIA NIH HHS R01 AG015819NIA NIH HHS R01 AG017917NIA NIH HHS R01 AG022018NIA NIH HHS R01 AG042210NIA NIH HHS R01 AG044546NIA NIH HHS R01 AG054047NIA NIH HHS R01 AG059716NIA NIH HHS R01 AG064614NIA NIH HHS R01 AG064877NIA NIH HHS R01 AG067505NIA NIH HHS R01 AG073439NIA NIH HHS R01 AG079280NIA NIH HHS RF1 AG053303NIA NIH HHS RF1 AG054047NIA NIH HHS RF1 AG054080NIA NIH HHS RF1 AG058501NIA NIH HHS RF1 AG074007NIA NIH HHS U01 AG006781NIA NIH HHS U01 AG024904NIA NIH HHS U01 AG052410NIA NIH HHS U01 AG058922NIA NIH HHS U01 AG068057NIA NIH HHS U01 AG072177NIA NIH HHS U19 AG024904NIA NIH HHS U19 AG032438NIA NIH HHS U19 AG066567NIA NIH HHS U19 AG074879NIA NIH HHS U24 AG041689NIA NIH HHS U24 AG056270NIA NIH HHS U24 AG072122NIA NIH HHS U24 AG074855U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging) R01AG044546
Abstract
Cerebrospinal fluid amyloid beta 42, total tau, and phosphorylated tau 181 are well accepted markers of Alzheimer's disease. These biomarkers better reflect disease pathogenesis compared to clinical diagnosis. Here, we perform a genome wide association study meta-analysis including 18,948 individuals of European ancestry and identify 12 genome-wide significant loci across all three biomarkers, eight of them novel. We replicate the association of biomarkers with APOE, CR1, GMNC/CCDC50 and C16orf95/MAP1LC3B. Novel loci include BIN1 for amyloid beta and GNA12, MS4A6A, SLCO1A2 with both total tau and phosphorylated tau 181, as well as additional loci on chr. 8, near ANGPT1 and chr. 9 near SMARCA2. We also demonstrate that these variants have significant association with Alzheimer's disease risk, disease progression and/or brain amyloidosis. The associated genes are implicated in lipid metabolism independent of APOE, coupled with autophagy and brain volume regulation driven by total tau and phosphorylated tau 181 dysregulation.
Indexed as
Alzheimer DiseaseAutophagyBrainLipid MetabolismAmyloid beta-PeptidesApolipoproteins EBiomarkersFemaleGenetic Predisposition to DiseaseGenome-Wide Association StudyHumansMalePolymorphism, Single Nucleotidetau ProteinsAmyloid beta-PeptidesApolipoproteins EBiomarkerstau Proteins
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