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Genome-wide meta-analysis for Alzheimer’s disease cerebrospinal fluid biomarkers
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...
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| Formato: | Online Artículo Texto |
| Lenguaje: | English |
| Publicado: |
Springer Berlin Heidelberg
2022
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| Materias: | |
| Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9547780/ https://www.ncbi.nlm.nih.gov/pubmed/36066633 http://dx.doi.org/10.1007/s00401-022-02454-z |
| _version_ | 1784805339006238720 |
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| author | Jansen, Iris E. van der Lee, Sven J. Gomez-Fonseca, Duber de Rojas, Itziar Dalmasso, Maria Carolina Grenier-Boley, Benjamin Zettergren, Anna Mishra, Aniket Ali, Muhammad Andrade, Victor Bellenguez, Céline Kleineidam, Luca Küçükali, Fahri Sung, Yun Ju Tesí, Niccolo Vromen, Ellen M. Wightman, Douglas P. Alcolea, Daniel Alegret, Montserrat Alvarez, Ignacio Amouyel, Philippe Athanasiu, Lavinia Bahrami, Shahram Bailly, Henri Belbin, Olivia Bergh, Sverre Bertram, Lars Biessels, Geert Jan Blennow, Kaj Blesa, Rafael Boada, Mercè Boland, Anne Buerger, Katharina Carracedo, Ángel Cervera-Carles, Laura Chene, Geneviève Claassen, Jurgen A. H. R. Debette, Stephanie Deleuze, Jean-Francois de Deyn, Peter Paul Diehl-Schmid, Janine Djurovic, Srdjan Dols-Icardo, Oriol Dufouil, Carole Duron, Emmanuelle Düzel, Emrah Fladby, Tormod Fortea, Juan Frölich, Lutz García-González, Pablo Garcia-Martinez, Maria Giegling, Ina Goldhardt, Oliver Gobom, Johan Grimmer, Timo Haapasalo, Annakaisa Hampel, Harald Hanon, Olivier Hausner, Lucrezia Heilmann-Heimbach, Stefanie Helisalmi, Seppo Heneka, Michael T. Hernández, Isabel Herukka, Sanna-Kaisa Holstege, Henne Jarholm, Jonas Kern, Silke Knapskog, Anne-Brita Koivisto, Anne M. Kornhuber, Johannes Kuulasmaa, Teemu Lage, Carmen Laske, Christoph Leinonen, Ville Lewczuk, Piotr Lleó, Alberto de Munain, Adolfo López Lopez-Garcia, Sara Maier, Wolfgang Marquié, Marta Mol, Merel O. Montrreal, Laura Moreno, Fermin Moreno-Grau, Sonia Nicolas, Gael Nöthen, Markus M. Orellana, Adelina Pålhaugen, Lene Papma, Janne M. Pasquier, Florence Perneczky, Robert Peters, Oliver Pijnenburg, Yolande A. L. Popp, Julius Posthuma, Danielle Pozueta, Ana Priller, Josef Puerta, Raquel Quintela, Inés Ramakers, Inez Rodriguez-Rodriguez, Eloy Rujescu, Dan Saltvedt, Ingvild Sanchez-Juan, Pascual Scheltens, Philip Scherbaum, Norbert Schmid, Matthias Schneider, Anja Selbæk, Geir Selnes, Per Shadrin, Alexey Skoog, Ingmar Soininen, Hilkka Tárraga, Lluís Teipel, Stefan Tijms, Betty Tsolaki, Magda Van Broeckhoven, Christine Van Dongen, Jasper van Swieten, John C. Vandenberghe, Rik Vidal, Jean-Sébastien Visser, Pieter J. Vogelgsang, Jonathan Waern, Margda Wagner, Michael Wiltfang, Jens Wittens, Mandy M. J. Zetterberg, Henrik Zulaica, Miren van Duijn, Cornelia M. Bjerke, Maria Engelborghs, Sebastiaan Jessen, Frank Teunissen, Charlotte E. Pastor, Pau Hiltunen, Mikko Ingelsson, Martin Andreassen, Ole A. Clarimón, Jordi Sleegers, Kristel Ruiz, Agustín Ramirez, Alfredo Cruchaga, Carlos Lambert, Jean-Charles van der Flier, Wiesje |
| author_facet | Jansen, Iris E. van der Lee, Sven J. Gomez-Fonseca, Duber de Rojas, Itziar Dalmasso, Maria Carolina Grenier-Boley, Benjamin Zettergren, Anna Mishra, Aniket Ali, Muhammad Andrade, Victor Bellenguez, Céline Kleineidam, Luca Küçükali, Fahri Sung, Yun Ju Tesí, Niccolo Vromen, Ellen M. Wightman, Douglas P. Alcolea, Daniel Alegret, Montserrat Alvarez, Ignacio Amouyel, Philippe Athanasiu, Lavinia Bahrami, Shahram Bailly, Henri Belbin, Olivia Bergh, Sverre Bertram, Lars Biessels, Geert Jan Blennow, Kaj Blesa, Rafael Boada, Mercè Boland, Anne Buerger, Katharina Carracedo, Ángel Cervera-Carles, Laura Chene, Geneviève Claassen, Jurgen A. H. R. Debette, Stephanie Deleuze, Jean-Francois de Deyn, Peter Paul Diehl-Schmid, Janine Djurovic, Srdjan Dols-Icardo, Oriol Dufouil, Carole Duron, Emmanuelle Düzel, Emrah Fladby, Tormod Fortea, Juan Frölich, Lutz García-González, Pablo Garcia-Martinez, Maria Giegling, Ina Goldhardt, Oliver Gobom, Johan Grimmer, Timo Haapasalo, Annakaisa Hampel, Harald Hanon, Olivier Hausner, Lucrezia Heilmann-Heimbach, Stefanie Helisalmi, Seppo Heneka, Michael T. Hernández, Isabel Herukka, Sanna-Kaisa Holstege, Henne Jarholm, Jonas Kern, Silke Knapskog, Anne-Brita Koivisto, Anne M. Kornhuber, Johannes Kuulasmaa, Teemu Lage, Carmen Laske, Christoph Leinonen, Ville Lewczuk, Piotr Lleó, Alberto de Munain, Adolfo López Lopez-Garcia, Sara Maier, Wolfgang Marquié, Marta Mol, Merel O. Montrreal, Laura Moreno, Fermin Moreno-Grau, Sonia Nicolas, Gael Nöthen, Markus M. Orellana, Adelina Pålhaugen, Lene Papma, Janne M. Pasquier, Florence Perneczky, Robert Peters, Oliver Pijnenburg, Yolande A. L. Popp, Julius Posthuma, Danielle Pozueta, Ana Priller, Josef Puerta, Raquel Quintela, Inés Ramakers, Inez Rodriguez-Rodriguez, Eloy Rujescu, Dan Saltvedt, Ingvild Sanchez-Juan, Pascual Scheltens, Philip Scherbaum, Norbert Schmid, Matthias Schneider, Anja Selbæk, Geir Selnes, Per Shadrin, Alexey Skoog, Ingmar Soininen, Hilkka Tárraga, Lluís Teipel, Stefan Tijms, Betty Tsolaki, Magda Van Broeckhoven, Christine Van Dongen, Jasper van Swieten, John C. Vandenberghe, Rik Vidal, Jean-Sébastien Visser, Pieter J. Vogelgsang, Jonathan Waern, Margda Wagner, Michael Wiltfang, Jens Wittens, Mandy M. J. Zetterberg, Henrik Zulaica, Miren van Duijn, Cornelia M. Bjerke, Maria Engelborghs, Sebastiaan Jessen, Frank Teunissen, Charlotte E. Pastor, Pau Hiltunen, Mikko Ingelsson, Martin Andreassen, Ole A. Clarimón, Jordi Sleegers, Kristel Ruiz, Agustín Ramirez, Alfredo Cruchaga, Carlos Lambert, Jean-Charles van der Flier, Wiesje |
| author_sort | Jansen, Iris E. |
| collection | PubMed |
| description | 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. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00401-022-02454-z. |
| format | Online Article Text |
| id | pubmed-9547780 |
| institution | National Center for Biotechnology Information |
| language | English |
| publishDate | 2022 |
| publisher | Springer Berlin Heidelberg |
| record_format | MEDLINE/PubMed |
| spelling | pubmed-95477802022-10-10 Genome-wide meta-analysis for Alzheimer’s disease cerebrospinal fluid biomarkers Jansen, Iris E. van der Lee, Sven J. Gomez-Fonseca, Duber de Rojas, Itziar Dalmasso, Maria Carolina Grenier-Boley, Benjamin Zettergren, Anna Mishra, Aniket Ali, Muhammad Andrade, Victor Bellenguez, Céline Kleineidam, Luca Küçükali, Fahri Sung, Yun Ju Tesí, Niccolo Vromen, Ellen M. Wightman, Douglas P. Alcolea, Daniel Alegret, Montserrat Alvarez, Ignacio Amouyel, Philippe Athanasiu, Lavinia Bahrami, Shahram Bailly, Henri Belbin, Olivia Bergh, Sverre Bertram, Lars Biessels, Geert Jan Blennow, Kaj Blesa, Rafael Boada, Mercè Boland, Anne Buerger, Katharina Carracedo, Ángel Cervera-Carles, Laura Chene, Geneviève Claassen, Jurgen A. H. R. Debette, Stephanie Deleuze, Jean-Francois de Deyn, Peter Paul Diehl-Schmid, Janine Djurovic, Srdjan Dols-Icardo, Oriol Dufouil, Carole Duron, Emmanuelle Düzel, Emrah Fladby, Tormod Fortea, Juan Frölich, Lutz García-González, Pablo Garcia-Martinez, Maria Giegling, Ina Goldhardt, Oliver Gobom, Johan Grimmer, Timo Haapasalo, Annakaisa Hampel, Harald Hanon, Olivier Hausner, Lucrezia Heilmann-Heimbach, Stefanie Helisalmi, Seppo Heneka, Michael T. Hernández, Isabel Herukka, Sanna-Kaisa Holstege, Henne Jarholm, Jonas Kern, Silke Knapskog, Anne-Brita Koivisto, Anne M. Kornhuber, Johannes Kuulasmaa, Teemu Lage, Carmen Laske, Christoph Leinonen, Ville Lewczuk, Piotr Lleó, Alberto de Munain, Adolfo López Lopez-Garcia, Sara Maier, Wolfgang Marquié, Marta Mol, Merel O. Montrreal, Laura Moreno, Fermin Moreno-Grau, Sonia Nicolas, Gael Nöthen, Markus M. Orellana, Adelina Pålhaugen, Lene Papma, Janne M. Pasquier, Florence Perneczky, Robert Peters, Oliver Pijnenburg, Yolande A. L. Popp, Julius Posthuma, Danielle Pozueta, Ana Priller, Josef Puerta, Raquel Quintela, Inés Ramakers, Inez Rodriguez-Rodriguez, Eloy Rujescu, Dan Saltvedt, Ingvild Sanchez-Juan, Pascual Scheltens, Philip Scherbaum, Norbert Schmid, Matthias Schneider, Anja Selbæk, Geir Selnes, Per Shadrin, Alexey Skoog, Ingmar Soininen, Hilkka Tárraga, Lluís Teipel, Stefan Tijms, Betty Tsolaki, Magda Van Broeckhoven, Christine Van Dongen, Jasper van Swieten, John C. Vandenberghe, Rik Vidal, Jean-Sébastien Visser, Pieter J. Vogelgsang, Jonathan Waern, Margda Wagner, Michael Wiltfang, Jens Wittens, Mandy M. J. Zetterberg, Henrik Zulaica, Miren van Duijn, Cornelia M. Bjerke, Maria Engelborghs, Sebastiaan Jessen, Frank Teunissen, Charlotte E. Pastor, Pau Hiltunen, Mikko Ingelsson, Martin Andreassen, Ole A. Clarimón, Jordi Sleegers, Kristel Ruiz, Agustín Ramirez, Alfredo Cruchaga, Carlos Lambert, Jean-Charles van der Flier, Wiesje Acta Neuropathol Original Paper 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. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00401-022-02454-z. Springer Berlin Heidelberg 2022-09-06 2022 /pmc/articles/PMC9547780/ /pubmed/36066633 http://dx.doi.org/10.1007/s00401-022-02454-z Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
| spellingShingle | Original Paper Jansen, Iris E. van der Lee, Sven J. Gomez-Fonseca, Duber de Rojas, Itziar Dalmasso, Maria Carolina Grenier-Boley, Benjamin Zettergren, Anna Mishra, Aniket Ali, Muhammad Andrade, Victor Bellenguez, Céline Kleineidam, Luca Küçükali, Fahri Sung, Yun Ju Tesí, Niccolo Vromen, Ellen M. Wightman, Douglas P. Alcolea, Daniel Alegret, Montserrat Alvarez, Ignacio Amouyel, Philippe Athanasiu, Lavinia Bahrami, Shahram Bailly, Henri Belbin, Olivia Bergh, Sverre Bertram, Lars Biessels, Geert Jan Blennow, Kaj Blesa, Rafael Boada, Mercè Boland, Anne Buerger, Katharina Carracedo, Ángel Cervera-Carles, Laura Chene, Geneviève Claassen, Jurgen A. H. R. Debette, Stephanie Deleuze, Jean-Francois de Deyn, Peter Paul Diehl-Schmid, Janine Djurovic, Srdjan Dols-Icardo, Oriol Dufouil, Carole Duron, Emmanuelle Düzel, Emrah Fladby, Tormod Fortea, Juan Frölich, Lutz García-González, Pablo Garcia-Martinez, Maria Giegling, Ina Goldhardt, Oliver Gobom, Johan Grimmer, Timo Haapasalo, Annakaisa Hampel, Harald Hanon, Olivier Hausner, Lucrezia Heilmann-Heimbach, Stefanie Helisalmi, Seppo Heneka, Michael T. Hernández, Isabel Herukka, Sanna-Kaisa Holstege, Henne Jarholm, Jonas Kern, Silke Knapskog, Anne-Brita Koivisto, Anne M. Kornhuber, Johannes Kuulasmaa, Teemu Lage, Carmen Laske, Christoph Leinonen, Ville Lewczuk, Piotr Lleó, Alberto de Munain, Adolfo López Lopez-Garcia, Sara Maier, Wolfgang Marquié, Marta Mol, Merel O. Montrreal, Laura Moreno, Fermin Moreno-Grau, Sonia Nicolas, Gael Nöthen, Markus M. Orellana, Adelina Pålhaugen, Lene Papma, Janne M. Pasquier, Florence Perneczky, Robert Peters, Oliver Pijnenburg, Yolande A. L. Popp, Julius Posthuma, Danielle Pozueta, Ana Priller, Josef Puerta, Raquel Quintela, Inés Ramakers, Inez Rodriguez-Rodriguez, Eloy Rujescu, Dan Saltvedt, Ingvild Sanchez-Juan, Pascual Scheltens, Philip Scherbaum, Norbert Schmid, Matthias Schneider, Anja Selbæk, Geir Selnes, Per Shadrin, Alexey Skoog, Ingmar Soininen, Hilkka Tárraga, Lluís Teipel, Stefan Tijms, Betty Tsolaki, Magda Van Broeckhoven, Christine Van Dongen, Jasper van Swieten, John C. Vandenberghe, Rik Vidal, Jean-Sébastien Visser, Pieter J. Vogelgsang, Jonathan Waern, Margda Wagner, Michael Wiltfang, Jens Wittens, Mandy M. J. Zetterberg, Henrik Zulaica, Miren van Duijn, Cornelia M. Bjerke, Maria Engelborghs, Sebastiaan Jessen, Frank Teunissen, Charlotte E. Pastor, Pau Hiltunen, Mikko Ingelsson, Martin Andreassen, Ole A. Clarimón, Jordi Sleegers, Kristel Ruiz, Agustín Ramirez, Alfredo Cruchaga, Carlos Lambert, Jean-Charles van der Flier, Wiesje Genome-wide meta-analysis for Alzheimer’s disease cerebrospinal fluid biomarkers |
| title | Genome-wide meta-analysis for Alzheimer’s disease cerebrospinal fluid biomarkers |
| title_full | Genome-wide meta-analysis for Alzheimer’s disease cerebrospinal fluid biomarkers |
| title_fullStr | Genome-wide meta-analysis for Alzheimer’s disease cerebrospinal fluid biomarkers |
| title_full_unstemmed | Genome-wide meta-analysis for Alzheimer’s disease cerebrospinal fluid biomarkers |
| title_short | Genome-wide meta-analysis for Alzheimer’s disease cerebrospinal fluid biomarkers |
| title_sort | genome-wide meta-analysis for alzheimer’s disease cerebrospinal fluid biomarkers |
| topic | Original Paper |
| url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9547780/ https://www.ncbi.nlm.nih.gov/pubmed/36066633 http://dx.doi.org/10.1007/s00401-022-02454-z |
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