Journal Articles Acta Neuropathologica Year : 2022

Genome-wide meta-analysis for Alzheimer's disease cerebrospinal fluid biomarkers

Iris E. Jansen , Sven J van der Lee , Duber Gomez-Fonseca , Itziar de Rojas , Maria Carolina Dalmasso , Benjamin Grenier-Boley , Anna Zettergren , Aniket Mishra , Muhammad Ali , Victor Andrade , Celine Bellenguez , Luca Kleineidam , Fahri Kucukali , Yun Ju Sung , Niccolo Tesi , Ellen M. Vromen , Douglas P. Wightman , Daniel Alcolea , Montserrat Alegret , Ignacio Alvarez , Philippe Amouyel , Lavinia Athanasiu , Shahram Bahrami , Henri Bailly (1) , Olivia Belbin , Sverre Bergh , Lars Bertram , Geert Jan Biessels , Kaj Blennow , Rafael Blesa , Merce Boada , Anne Boland (2) , Katharina Buerger , Angel Carracedo , Laura Cervera-Carles , Genevieve Chene (3) , Jurgen A. H. R. Claassen , Stephanie Debette (3) , Jean-Francois Deleuze (2) , Peter Paul de Deyn , Janine Diehl-Schmid , Srdjan Djurovic , Oriol Dols-Icardo , Carole Dufouil (3) , Emmanuelle Duron , Emrah Duzel , Tormod Fladby , Juan Fortea , Lutz Frolich , Pablo Garcia-Gonzalez , Maria Garcia-Martinez , Ina Giegling , Oliver Goldhardt , Johan Gobom , Timo Grimmer , Annakaisa Haapasalo , Harald Hampel , Olivier Hanon (1) , Lucrezia Hausner , Stefanie Heilmann-Heimbach , Seppo Helisalmi , Michael T. Heneka , Isabel Hernandez , Sanna-Kaisa Herukka , Henne Holstege , Jonas Jarholm , Silke Kern , Anne-Brita Knapskog , Anne M. Koivisto , Johannes Kornhuber , Teemu Kuulasmaa , Carmen Lage , Christoph Laske , Ville Leinonen , Piotr Lewczuk , Alberto Lleo , Adolfo Lopez de Munain , Sara Lopez-Garcia , Wolfgang Maier , Marta Marquie , Merel O. Mol , Laura Montrreal , Fermin Moreno , Sonia Moreno-Grau , Gael Nicolas , Markus M Nothen , Adelina Orellana , Lene Palhaugen , Janne M. Papma , Florence Pasquier , Robert Perneczky , Oliver Peters , Yolande A. L. Pijnenburg , Julius Popp , Danielle Posthuma , Ana Pozueta , Josef Priller , Raquel Puerta , Ines Quintela , Inez Ramakers , Eloy Rodriguez-Rodriguez , Dan Rujescu , Ingvild Saltvedt , Pascual Sanchez-Juan , Philip Scheltens , Norbert Scherbaum , Matthias Schmid , Anja Schneider , Geir Selbaek , Per Selnes , Alexey Shadrin , Ingmar Skoog , Hilkka Soininen , Lluis Tarraga , Stefan Teipel , Betty Tijms , Magda Tsolaki , Christine van Broeckhoven , Jasper van Dongen , John C. van Swieten , Rik Vandenberghe , Jean-Sebastien Vidal (1) , Pieter J. Visser , Jonathan Vogelgsang , Margda Waern , Michael Wagner , Jens Wiltfang , Mandy M. J. Wittens , Henrik Zetterberg , Miren Zulaica , Cornelia M. van Duijn , Maria Bjerke , Sebastiaan Engelborghs , Frank Jessen , Charlotte E. Teunissen , Pau Pastor , Mikko Hiltunen , Martin Ingelsson , Ole A. Andreassen , Jordi Clarimon , Kristel Sleegers , Agustin Ruiz , Alfredo Ramirez , Carlos Cruchaga , Jean-Charles Lambert , Wiesje van der Flier
Iris E. Jansen
  • Function : Author
Sven J van der Lee
  • Function : Author
Duber Gomez-Fonseca
  • Function : Author
Itziar de Rojas
  • Function : Author
Maria Carolina Dalmasso
  • Function : Author
Benjamin Grenier-Boley
  • Function : Author
Anna Zettergren
  • Function : Author
Aniket Mishra
  • Function : Author
Muhammad Ali
  • Function : Author
Victor Andrade
  • Function : Author
Celine Bellenguez
Luca Kleineidam
  • Function : Author
Fahri Kucukali
  • Function : Author
Yun Ju Sung
  • Function : Author
Niccolo Tesi
  • Function : Author
Ellen M. Vromen
  • Function : Author
Douglas P. Wightman
  • Function : Author
Daniel Alcolea
  • Function : Author
Montserrat Alegret
  • Function : Author
Ignacio Alvarez
  • Function : Author
Philippe Amouyel
  • Function : Author
Lavinia Athanasiu
  • Function : Author
Shahram Bahrami
  • Function : Author
Olivia Belbin
  • Function : Author
Sverre Bergh
  • Function : Author
Lars Bertram
  • Function : Author
Geert Jan Biessels
  • Function : Author
Kaj Blennow
  • Function : Author
Rafael Blesa
  • Function : Author
Merce Boada
  • Function : Author
Katharina Buerger
  • Function : Author
Angel Carracedo
  • Function : Author
Laura Cervera-Carles
  • Function : Author
Genevieve Chene
Jurgen A. H. R. Claassen
  • Function : Author
Peter Paul de Deyn
  • Function : Author
Janine Diehl-Schmid
  • Function : Author
Srdjan Djurovic
  • Function : Author
Oriol Dols-Icardo
  • Function : Author
Emmanuelle Duron
  • Function : Author
Emrah Duzel
  • Function : Author
Tormod Fladby
  • Function : Author
Juan Fortea
  • Function : Author
Lutz Frolich
  • Function : Author
Pablo Garcia-Gonzalez
  • Function : Author
Maria Garcia-Martinez
  • Function : Author
Ina Giegling
  • Function : Author
Oliver Goldhardt
  • Function : Author
Johan Gobom
  • Function : Author
Timo Grimmer
  • Function : Author
Annakaisa Haapasalo
  • Function : Author
Harald Hampel
Lucrezia Hausner
  • Function : Author
Stefanie Heilmann-Heimbach
  • Function : Author
Seppo Helisalmi
  • Function : Author
Michael T. Heneka
  • Function : Author
Isabel Hernandez
  • Function : Author
Sanna-Kaisa Herukka
  • Function : Author
Henne Holstege
  • Function : Author
Jonas Jarholm
  • Function : Author
Silke Kern
  • Function : Author
Anne-Brita Knapskog
  • Function : Author
Anne M. Koivisto
  • Function : Author
Johannes Kornhuber
  • Function : Author
Teemu Kuulasmaa
  • Function : Author
Carmen Lage
  • Function : Author
Christoph Laske
  • Function : Author
Ville Leinonen
  • Function : Author
Piotr Lewczuk
  • Function : Author
Alberto Lleo
  • Function : Author
Adolfo Lopez de Munain
  • Function : Author
Sara Lopez-Garcia
  • Function : Author
Wolfgang Maier
  • Function : Author
Marta Marquie
  • Function : Author
Merel O. Mol
  • Function : Author
Laura Montrreal
  • Function : Author
Fermin Moreno
  • Function : Author
Sonia Moreno-Grau
  • Function : Author
Gael Nicolas
  • Function : Author
Markus M Nothen
  • Function : Author
Adelina Orellana
  • Function : Author
Lene Palhaugen
  • Function : Author
Janne M. Papma
  • Function : Author
Florence Pasquier
Robert Perneczky
  • Function : Author
Oliver Peters
  • Function : Author
Yolande A. L. Pijnenburg
  • Function : Author
Julius Popp
  • Function : Author
Danielle Posthuma
  • Function : Author
Ana Pozueta
  • Function : Author
Josef Priller
  • Function : Author
Raquel Puerta
  • Function : Author
Ines Quintela
  • Function : Author
Inez Ramakers
  • Function : Author
Eloy Rodriguez-Rodriguez
  • Function : Author
Dan Rujescu
  • Function : Author
Ingvild Saltvedt
  • Function : Author
Pascual Sanchez-Juan
  • Function : Author
Philip Scheltens
  • Function : Author
Norbert Scherbaum
  • Function : Author
Matthias Schmid
  • Function : Author
Anja Schneider
  • Function : Author
Geir Selbaek
  • Function : Author
Per Selnes
  • Function : Author
Alexey Shadrin
  • Function : Author
Ingmar Skoog
  • Function : Author
Hilkka Soininen
  • Function : Author
Lluis Tarraga
  • Function : Author
Stefan Teipel
  • Function : Author
Betty Tijms
  • Function : Author
Magda Tsolaki
  • Function : Author
Christine van Broeckhoven
  • Function : Author
Jasper van Dongen
  • Function : Author
John C. van Swieten
  • Function : Author
Rik Vandenberghe
  • Function : Author
Pieter J. Visser
  • Function : Author
Jonathan Vogelgsang
  • Function : Author
Margda Waern
  • Function : Author
Michael Wagner
  • Function : Author
Jens Wiltfang
  • Function : Author
Mandy M. J. Wittens
  • Function : Author
Henrik Zetterberg
  • Function : Author
Miren Zulaica
  • Function : Author
Cornelia M. van Duijn
  • Function : Author
Maria Bjerke
  • Function : Author
Sebastiaan Engelborghs
  • Function : Author
Frank Jessen
  • Function : Author
Charlotte E. Teunissen
  • Function : Author
Pau Pastor
  • Function : Author
Mikko Hiltunen
  • Function : Author
Martin Ingelsson
  • Function : Author
Ole A. Andreassen
  • Function : Author
Jordi Clarimon
  • Function : Author
Kristel Sleegers
  • Function : Author
Agustin Ruiz
  • Function : Author
Alfredo Ramirez
  • Function : Author
Carlos Cruchaga
  • Function : Author
Jean-Charles Lambert
  • Function : Author
Wiesje van der Flier
  • Function : Author

Abstract

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.

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hal-03902957 , version 1 (16-12-2022)

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Iris E. Jansen, Sven J van der Lee, Duber Gomez-Fonseca, Itziar de Rojas, Maria Carolina Dalmasso, et al.. Genome-wide meta-analysis for Alzheimer's disease cerebrospinal fluid biomarkers. Acta Neuropathologica, 2022, 144 (5), pp.821-842. ⟨10.1007/s00401-022-02454-z⟩. ⟨hal-03902957⟩
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