Genome-wide meta-analysis for Alzheimer’s disease cerebrospinal fluid biomarkers,Acta Neuropathologica

当前位置： X-MOL 学术 › Acta Neuropathol. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

Genome-wide meta-analysis for Alzheimer’s disease cerebrospinal fluid biomarkers
Acta Neuropathologica ( IF 12.7 ) Pub Date : 2022-09-06 , DOI: 10.1007/s00401-022-02454-z
Iris E Jansen _{1,

2,

3} , Sven J van der Lee _{1,

2,

4} , Duber Gomez-Fonseca _{5,

6,

7} , Itziar de Rojas _{8,

9} , Maria Carolina Dalmasso _{10,

11} , Benjamin Grenier-Boley ₁₂ , Anna Zettergren ₁₃ , Aniket Mishra ₁₄ , Muhammad Ali _{5,

6,

7} , Victor Andrade _{10,

15} , Céline Bellenguez ₁₂ , Luca Kleineidam _{10,

15,

16} , Fahri Küçükali _{17,

18} , Yun Ju Sung _{5,

6,

7} , Niccolo Tesí _{1,

2,

4} , Ellen M Vromen _{1,

2} , Douglas P Wightman ₃ , Daniel Alcolea _{9,

19} , Montserrat Alegret _{8,

9} , Ignacio Alvarez _{20,

21} , Philippe Amouyel ₁₂ , Lavinia Athanasiu ₂₂ , Shahram Bahrami ₂₂ , Henri Bailly ₂₃ , Olivia Belbin _{9,

19} , Sverre Bergh _{24,

25} , Lars Bertram ₂₆ , Geert Jan Biessels ₂₇ , Kaj Blennow _{28,

29} , Rafael Blesa _{9,

19} , Mercè Boada _{8,

9} , Anne Boland ₃₀ , Katharina Buerger _{31,

32} , Ángel Carracedo _{33,

34} , Laura Cervera-Carles _{9,

19} , Geneviève Chene _{14,

35} , Jurgen A H R Claassen _{36,

37} , Stephanie Debette _{14,

35,

38} , Jean-Francois Deleuze ₃₀ , Peter Paul de Deyn ₃₉ , Janine Diehl-Schmid _{40,

41} , Srdjan Djurovic _{42,

43} , Oriol Dols-Icardo _{9,

19} , Carole Dufouil _{14,

44} , Emmanuelle Duron ₄₅ , Emrah Düzel _{46,

47} , , Tormod Fladby _{48,

49} , Juan Fortea _{9,

19} , Lutz Frölich ₅₀ , Pablo García-González _{8,

9} , Maria Garcia-Martinez ₅₁ , Ina Giegling ₅₂ , Oliver Goldhardt ₄₀ , Johan Gobom ₂₉ , Timo Grimmer ₄₀ , Annakaisa Haapasalo ₅₃ , Harald Hampel _{54,

55} , Olivier Hanon _{23,

56} , Lucrezia Hausner ₅₀ , Stefanie Heilmann-Heimbach ₅₇ , Seppo Helisalmi ₅₈ , Michael T Heneka _{15,

16} , Isabel Hernández _{8,

9} , Sanna-Kaisa Herukka ₅₉ , Henne Holstege _{1,

2,

4} , Jonas Jarholm ₄₉ , Silke Kern _{13,

60} , Anne-Brita Knapskog ₆₁ , Anne M Koivisto _{59,

62,

63} , Johannes Kornhuber ₆₄ , Teemu Kuulasmaa ₆₅ , Carmen Lage _{51,

66} , Christoph Laske _{67,

68} , Ville Leinonen _{69,

70} , Piotr Lewczuk _{64,

71} , Alberto Lleó _{9,

19} , Adolfo López de Munain _{9,

72,

73,

74} , Sara Lopez-Garcia ₅₁ , Wolfgang Maier ₁₅ , Marta Marquié _{8,

9} , Merel O Mol ₇₅ , Laura Montrreal ₈ , Fermin Moreno _{9,

72,

73} , Sonia Moreno-Grau _{8,

9} , Gael Nicolas ₇₆ , Markus M Nöthen ₅₇ , Adelina Orellana _{8,

9} , Lene Pålhaugen _{48,

49} , Janne M Papma ₇₅ , Florence Pasquier ₁₂ , Robert Perneczky _{31,

77,

78,

79} , Oliver Peters _{46,

80} , Yolande A L Pijnenburg _{1,

2} , Julius Popp _{81,

82} , Danielle Posthuma ₃ , Ana Pozueta ₅₁ , Josef Priller _{80,

83,

84} , Raquel Puerta ₈ , Inés Quintela ₃₃ , Inez Ramakers ₈₅ , Eloy Rodriguez-Rodriguez ₅₁ , Dan Rujescu ₅₂ , Ingvild Saltvedt _{86,

87} , Pascual Sanchez-Juan ₈₈ , Philip Scheltens _{1,

2} , Norbert Scherbaum ₈₉ , Matthias Schmid ₉₀ , Anja Schneider _{15,

16} , Geir Selbæk _{25,

48,

61} , Per Selnes ₄₉ , Alexey Shadrin ₂₂ , Ingmar Skoog _{13,

60} , Hilkka Soininen ₅₉ , Lluís Tárraga _{8,

9} , Stefan Teipel _{91,

92} , , Betty Tijms _{1,

2} , Magda Tsolaki ₉₃ , Christine Van Broeckhoven _{18,

94} , Jasper Van Dongen _{17,

18} , John C van Swieten ₇₅ , Rik Vandenberghe _{95,

96} , Jean-Sébastien Vidal ₂₃ , Pieter J Visser _{1,

2,

97,

98} , Jonathan Vogelgsang _{99,

100} , Margda Waern _{13,

101} , Michael Wagner _{15,

16} , Jens Wiltfang _{99,

102,

103} , Mandy M J Wittens _{18,

104} , Henrik Zetterberg _{28,

29,

105,

106,

107} , Miren Zulaica _{9,

72,

73} , Cornelia M van Duijn _{108,

109} , Maria Bjerke _{18,

104,

110} , Sebastiaan Engelborghs _{18,

104,

110,

111} , Frank Jessen _{16,

112,

113} , Charlotte E Teunissen _{2,

114} , Pau Pastor ₁₁₅ , Mikko Hiltunen ₁₁₆ , Martin Ingelsson _{117,

118,

119} , Ole A Andreassen _{22,

120} , Jordi Clarimón _{9,

19} , Kristel Sleegers _{17,

18} , Agustín Ruiz _{8,

9} , Alfredo Ramirez _{10,

15,

16,

113,

121} , Carlos Cruchaga _{5,

6,

7} , Jean-Charles Lambert ₁₂ , Wiesje van der Flier _{1,

2}

Affiliation

Alzheimer Center Amsterdam, Neurology, Vrije Universiteit Amsterdam, Amsterdam UMC Location VUmc, Amsterdam, The Netherlands.
Amsterdam Neuroscience, Neurodegeneration, Amsterdam, The Netherlands.
Department of Complex Trait Genetics, Center for Neurogenomics and Cognitive Research, Amsterdam Neuroscience, VU Amsterdam, Amsterdam, The Netherlands.
Section Genomics of Neurodegenerative Diseases and Aging, Human Genetics, Vrije Universiteit Amsterdam, Amsterdam UMC location VUmc, Amsterdam, The Netherlands.
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.
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.
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.
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.
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.
University of Bordeaux, Inserm, Bordeaux Population Health Research Center, Team VINTAGE, UMR 1219, 33000, Bordeaux, France.
Department of Neurodegenerative Diseases and Geriatric Psychiatry, University Hospital Bonn, Medical Faculty, Bonn, Germany.
German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany.
Complex Genetics of Alzheimer's Disease Group, VIB Center for Molecular Neurology, VIB, Antwerp, Belgium.
Department of Biomedical Sciences, University of Antwerp, Antwerp, Belgium.
Sant Pau Memory Unit, Department of Neurology, Institut d'Investigacions Biomèdiques Sant Pau - Hospital de Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain.
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.
NORMENT Centre, Institute of Clinical Medicine, University of Oslo and Division of Mental Health, Oslo, Norway.
Université Paris Cité, EA4468, Maladie d'Alzheimer, F-75013 Paris, France.
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.
Lübeck Interdisciplinary Platform for Genome Analytics, University of Lübeck, Lübeck, Germany.
Department of Neurology, UMC Utrecht Brain Center, Utrecht, The Netherlands.
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.
Université Paris-Saclay, CEA, Centre National de Recherche en Génomique Humaine, 91057, Evry, France.
German Center for Neurodegenerative Diseases (DZNE, Munich), Munich, Germany.
Institute for Stroke and Dementia Research (ISD), University Hospital, LMU Munich, Munich, Germany.
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.
Department of Neurology, CHU de Bordeaux, 33000, Bordeaux, France.
Radboudumc Alzheimer Center, Department of Geriatrics, Radboud University Medical Center, Nijmegen, The Netherlands.
Donders Center for Medical Neuroscience, Nijmegen, The Netherlands.
Department of Neurology, Boston University School of Medicine, Boston, MA, 2115, USA.
Department of Neurology and Alzheimer Center Groningen, University Medical Center Groningen, Groningen, The Netherlands.
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.
Department of Medical Genetics, Oslo University Hospital, Oslo, Norway.
Department of Clinical Science, NORMENT Centre, University of Bergen, Bergen, Norway.
Pôle de Santé Publique Centre Hospitalier Universitaire (CHU) de Bordeaux, Bordeaux, France.
Univerisité Paris-Saclay. Inserm 1178 MOODS, Paris, France.
German Center for Neurodegenerative Diseases (DZNE), Magdeburg, Germany.
Institute of Cognitive Neurology and Dementia Research (IKND), Otto-von-Guericke University, Magdeburg, Germany.
Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
Department of Neurology, Akershus University Hospital, Lorenskog, Norway.
Department of Geriatric Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg, Germany.
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.
Division of General Psychiatry, Department of Psychiatry and Psychotherapy, Medical University of Vienna, Vienna, Austria.
A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland.
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.
Service gériatrie, Centre Mémoire de Ressources et Recherches Ile de France-Broca, AP-HP, Hôpital Broca, F-75013, Paris, France.
Institute of Human Genetics, University of Bonn, School of Medicine and University Hospital Bonn, 53127, Bonn, Germany.
Institute of Clinical Medicine, Internal Medicine, University of Eastern Finland, Kuopio, Finland.
Department of Neurology, Institute of Clinical Medicine, University of Eastern Finland, Kuopio, Finland.
Region Västra Götaland, Sahlgrenska University Hospital, Psychiatry, Cognition and Old Age Psychiatry Clinic, Gothenburg, Sweden.
Department of Geriatric Medicine, Oslo University Hospital, Oslo, Norway.
Department of Neurology, Kuopio University Hospital, Kuopio, Finland.
Department of Neurology, Helsinki University Hospital, Helsinki, Finland.
Department of Psychiatry and Psychotherapy, Universitätsklinikum Erlangen, and Friedrich-Alexander Universität Erlangen-Nürnberg, Erlangen, Germany.
Bioinformatics Center, Institute of Biomedicine, University of Eastern Finland, Kuopio, Finland.
Atlantic Fellow at the Global Brain Health Institute (GBHI) -, University of California, San Francisco, USA.
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.
Institute of Clinical Medicine, Neurosurgery, University of Eastern Finland, Kuopio, Finland.
Department of Neurosurgery, Kuopio University Hospital, Kuopio, Finland.
Department of Neurodegeneration Diagnostics, Medical University of Białystok, Białystok, Poland.
Hospital Universitario Donostia-OSAKIDETZA, Donostia, Spain.
Instituto Biodonostia, San Sebastián, Spain.
University of The Basque Country, San Sebastian, Spain.
Department of Neurology and Alzheimer Center Erasmus MC, Erasmus MC University Medical Center, Rotterdam, The Netherlands.
Department of Genetics and CNR-MAJ, Normandie Univ, UNIROUEN, Inserm U1245 and CHU Rouen, Rouen, France.
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.
German Center for Neurodegenerative Diseases (DZNE), Berlin, Germany.
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.
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.
Department of Psychiatry and Neuropsychologie, Alzheimer Center Limburg, Maastricht University, Maastricht, The Netherlands.
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.
Alzheimer's Centre Reina Sofia-CIEN Foundation-ISCIII, 28031, Madrid, Spain.
Department of Psychiatry and Psychotherapy, Medical Faculty, LVR-Hospital Essen, University of Duisburg-Essen, Essen, Germany.
Institute of Medical Biometry, Informatics and Epidemiology, University Hospital of Bonn, Bonn, Germany.
German Center for Neurodegenerative Diseases (DZNE), Rostock, Germany.
Department of Psychosomatic Medicine, Rostock University Medical Center, Gehlsheimer Str. 20, 18147, Rostock, Germany.
1st Department of Neurology, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, Thessaloniki, Makedonia, Greece.
Neurodegenerative Brain Diseases Group, VIB Center for Molecular Neurology, VIB, Antwerp, Belgium.
Neurology, University Hospitals Leuven, Leuven, Belgium.
Laboratory for Cognitive Neurology, Department of Neurosciences, Leuven Brain Institute, Leuven, Belgium.
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.
Department of Psychiatry and Psychotherapy, University Medical Center Goettingen, Göttingen, Germany.
Department of Psychiatry, Harvard Medical School, McLean Hospital, Belmont, MA, USA.
Region Västra Götaland, Sahlgrenska University Hospital, Psychiatry, Psychosis Clinic, Gothenburg, Sweden.
German Center for Neurodegenerative Diseases (DZNE), Göttingen, Germany.
Medical Science Department, iBiMED, Aveiro, Portugal.
Center for Neurosciences (C4N), Vrije Universiteit Brussel, Brussels, Belgium.
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.
Department of Epidemiology, ErasmusMC, Rotterdam, The Netherlands.
Nuffield Department of Population Health, Oxford University, Oxford, UK.
Laboratory of Neurochemistry, Universitair Ziekenhuis Brussel, Brussels, Belgium.
Department of Neurology, Universitair Ziekenhuis Brussel, Brussels, Belgium.
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.
Neurochemistry Lab, Department of Clinical Chemistry, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam UMC, Amsterdam, The Netherlands.
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.
Institute of Biomedicine, University of Eastern Finland, Kuopio, Finland.
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.
Addiction, Oslo University Hospital, 0407, Oslo, Norway.
Department of Psychiatry, Glenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases, San Antonio, TX, USA.

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.

中文翻译：

阿尔茨海默病脑脊液生物标志物的全基因组荟萃分析

脑脊液 (CSF) 中的淀粉样蛋白 42 (Aβ42) 和磷酸化 tau (pTau) 水平比临床诊断更直接地反映了阿尔茨海默病 (AD) 发病机制的核心特征。由欧洲阿尔茨海默病和痴呆症生物库 (EADB) 发起，建立了 CSF 生物标志物遗传学方面最大的合作努力，包括 31 个队列，共有 13,116 人（发现n = 8074；复制n = 5042 人）。除了APOE基因座外，还观察到与其他两个公认的 AD 风险基因座的新关联；CR1显示为 Aβ42 的轨迹和pTau 的BIN1。GMNC和C16orf95被进一步确定为 pTau 的基因座，后者是新的。聚类方法探索了所有已知 AD 风险位点对 CSF 蛋白水平的影响，揭示了 4 个生物学类别，表明多个 Aβ42 和 pTau 相关生物学途径参与 AD 的病因学。在功能性后续分析中，GMNC和C16orf95均与侧脑室容积相关，这意味着 tau 水平和脑室容积的遗传病因学存在重叠。

更新日期：2022-09-07

点击分享查看原文

点击收藏

公开下载

阅读更多本刊最新论文本刊介绍/投稿指南

全部期刊列表>>