Multiancestry analysis of the HLA locus in Alzheimer's and Parkinson's diseases uncovers a shared adaptive immune response mediated by HLA-DRB1*04 subtypes
dc.date.accessioned | 2024-02-20T08:47:23Z | |
dc.date.available | 2024-02-20T08:47:23Z | |
dc.date.created | 2023-10-18T14:49:23Z | |
dc.date.issued | 2023 | |
dc.identifier.citation | Le Guen, Yann Luo, Guo Ambati, Aditya Damotte, Vincent Jansen, Iris Yu, Eric Nicolas, Aude de Rojas, Itziar Peixoto Leal, Thiago Miyashita, Akinori Bellenguez, Céline Lian, Michelle Mulan Parveen, Kayenat Morizono, Takashi Park, Hyeonseul Grenier-Boley, Benjamin Naito, Tatsuhiko Küçükali, Fahri Talyansky, Seth D. Yogeshwar, Selina Maria Sempere, Vicente Satake, Wataru Alvarez, Victoria Arosio, Beatrice Belloy, Michael E. Benussi, Luisa Boland, Anne Borroni, Barbara Bullido, María J Caffarra, Paolo Clarimon, Jordi Daniele, Antonio Darling, Daniel Debette, Stéphanie Deleuze, Jean-François Dichgans, Martin Dufouil, Carole During, Emmanuel Düzel, Emrah Galimberti, Daniela Garcia-Ribas, Guillermo García-Alberca, José María García-González, Pablo Giedraitis, Vilmantas Goldhardt, Oliver Graff, Caroline Grünblatt, Edna Hanon, Olivier Hausner, Lucrezia Heilmann-Heimbach, Stefanie Holstege, Henne Hort, Jakub Jung, Yoo Jin Jürgen, Deckert Kern, Silke Kuulasmaa, Teemu Lee, Kun Ho Lin, Ling Masullo, Carlo Mecocci, Patrizia Mehrabian, Shima de Mendonça, Alexandre Boada, Mercè Mir, Pablo Moebus, Susanne Moreno, Fermin Nacmias, Benedetta Nicolas, Gael Niida, Shumpei Nordestgaard, Børge G Papenberg, Goran Papma, Janne Parnetti, Lucilla Pasquier, Florence Pastor, Pau Peters, Oliver Pijnenburg, Yolande A L Piñol-Ripoll, Gerard Popp, Julius Porcel, Laura Molina Puerta, Raquel Pérez-Tur, Jordi Rainero, Innocenzo Ramakers, Inez Real, Luis M. Riedel-Heller, Steffi Rodriguez-Rodriguez, Eloy Ross, Owen A. Luís Royo, Jose Rujescu, Dan Scarmeas, Nikolaos Scheltens, Philip Scherbaum, Norbert Schneider, Anja Seripa, Davide Skoog, Ingmar Solfrizzi, Vincenzo Spalletta, Gianfranco Squassina, Alessio van Swieten, John Sánchez-Valle, Raquel Tan, Eng-King Tegos, Thomas Teunissen, Charlotte Thomassen, Jesper Qvist Tremolizzo, Lucio Vyhnalek, Martin Verhey, Frans Waern, Margda Wiltfang, Jens Zhang, Jing Zetterberg, Henrik Blennow, Kaj He, Zihuai Williams, Julie Amouyel, Philippe Jessen, Frank Kehoe, Patrick G. Andreassen, Ole Van Duin, Cornelia Tsolaki, Magda Sánchez-Juan, Pascual Frikke-Schmidt, Ruth Sleegers, Kristel Toda, Tatsushi Zettergren, Anna Ingelsson, Martin Okada, Yukinori Rossi, Giacomina Hiltunen, Mikko Gim, Jungsoo Ozaki, Kouichi Sims, Rebecca Foo, Jia Nee van der Flier, Wiesje Ikeuchi, Takeshi Ramirez, Alfredo Mata, Ignacio Ruiz, Agustín Gan-Or, Ziv Lambert, Jean-Charles Greicius, Michael D. Mignot, Emmanuel . Multiancestry analysis of the HLA locus in Alzheimer's and Parkinson's diseases uncovers a shared adaptive immune response mediated by HLA-DRB1*04 subtypes. Proceedings of the National Academy of Sciences of the United States of America. 2023, 120(36) | |
dc.identifier.uri | http://hdl.handle.net/10852/108332 | |
dc.description.abstract | Across multiancestry groups, we analyzed Human Leukocyte Antigen (HLA) associations in over 176,000 individuals with Parkinson’s disease (PD) and Alzheimer’s disease (AD) versus controls. We demonstrate that the two diseases share the same protective association at the HLA locus. HLA-specific fine-mapping showed that hierarchical protective effects of HLA-DRB1*04 subtypes best accounted for the association, strongest with HLA-DRB1*04:04 and HLA-DRB1*04:07, and intermediary with HLA-DRB1*04:01 and HLA-DRB1*04:03. The same signal was associated with decreased neurofibrillary tangles in postmortem brains and was associated with reduced tau levels in cerebrospinal fluid and to a lower extent with increased Aβ42. Protective HLA-DRB1*04 subtypes strongly bound the aggregation-prone tau PHF6 sequence, however only when acetylated at a lysine (K311), a common posttranslational modification central to tau aggregation. An HLA-DRB1*04-mediated adaptive immune response decreases PD and AD risks, potentially by acting against tau, offering the possibility of therapeutic avenues. | |
dc.language | EN | |
dc.publisher | The National Academy of Sciences | |
dc.rights | Attribution 4.0 International | |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0/ | |
dc.title | Multiancestry analysis of the HLA locus in Alzheimer's and Parkinson's diseases uncovers a shared adaptive immune response mediated by HLA-DRB1*04 subtypes | |
dc.title.alternative | ENEngelskEnglishMultiancestry analysis of the HLA locus in Alzheimer's and Parkinson's diseases uncovers a shared adaptive immune response mediated by HLA-DRB1*04 subtypes | |
dc.type | Journal article | |
dc.creator.author | Le Guen, Yann | |
dc.creator.author | Luo, Guo | |
dc.creator.author | Ambati, Aditya | |
dc.creator.author | Damotte, Vincent | |
dc.creator.author | Jansen, Iris | |
dc.creator.author | Yu, Eric | |
dc.creator.author | Nicolas, Aude | |
dc.creator.author | de Rojas, Itziar | |
dc.creator.author | Peixoto Leal, Thiago | |
dc.creator.author | Miyashita, Akinori | |
dc.creator.author | Bellenguez, Céline | |
dc.creator.author | Lian, Michelle Mulan | |
dc.creator.author | Parveen, Kayenat | |
dc.creator.author | Morizono, Takashi | |
dc.creator.author | Park, Hyeonseul | |
dc.creator.author | Grenier-Boley, Benjamin | |
dc.creator.author | Naito, Tatsuhiko | |
dc.creator.author | Küçükali, Fahri | |
dc.creator.author | Talyansky, Seth D. | |
dc.creator.author | Yogeshwar, Selina Maria | |
dc.creator.author | Sempere, Vicente | |
dc.creator.author | Satake, Wataru | |
dc.creator.author | Alvarez, Victoria | |
dc.creator.author | Arosio, Beatrice | |
dc.creator.author | Belloy, Michael E. | |
dc.creator.author | Benussi, Luisa | |
dc.creator.author | Boland, Anne | |
dc.creator.author | Borroni, Barbara | |
dc.creator.author | Bullido, María J | |
dc.creator.author | Caffarra, Paolo | |
dc.creator.author | Clarimon, Jordi | |
dc.creator.author | Daniele, Antonio | |
dc.creator.author | Darling, Daniel | |
dc.creator.author | Debette, Stéphanie | |
dc.creator.author | Deleuze, Jean-François | |
dc.creator.author | Dichgans, Martin | |
dc.creator.author | Dufouil, Carole | |
dc.creator.author | During, Emmanuel | |
dc.creator.author | Düzel, Emrah | |
dc.creator.author | Galimberti, Daniela | |
dc.creator.author | Garcia-Ribas, Guillermo | |
dc.creator.author | García-Alberca, José María | |
dc.creator.author | García-González, Pablo | |
dc.creator.author | Giedraitis, Vilmantas | |
dc.creator.author | Goldhardt, Oliver | |
dc.creator.author | Graff, Caroline | |
dc.creator.author | Grünblatt, Edna | |
dc.creator.author | Hanon, Olivier | |
dc.creator.author | Hausner, Lucrezia | |
dc.creator.author | Heilmann-Heimbach, Stefanie | |
dc.creator.author | Holstege, Henne | |
dc.creator.author | Hort, Jakub | |
dc.creator.author | Jung, Yoo Jin | |
dc.creator.author | Jürgen, Deckert | |
dc.creator.author | Kern, Silke | |
dc.creator.author | Kuulasmaa, Teemu | |
dc.creator.author | Lee, Kun Ho | |
dc.creator.author | Lin, Ling | |
dc.creator.author | Masullo, Carlo | |
dc.creator.author | Mecocci, Patrizia | |
dc.creator.author | Mehrabian, Shima | |
dc.creator.author | de Mendonça, Alexandre | |
dc.creator.author | Boada, Mercè | |
dc.creator.author | Mir, Pablo | |
dc.creator.author | Moebus, Susanne | |
dc.creator.author | Moreno, Fermin | |
dc.creator.author | Nacmias, Benedetta | |
dc.creator.author | Nicolas, Gael | |
dc.creator.author | Niida, Shumpei | |
dc.creator.author | Nordestgaard, Børge G | |
dc.creator.author | Papenberg, Goran | |
dc.creator.author | Papma, Janne | |
dc.creator.author | Parnetti, Lucilla | |
dc.creator.author | Pasquier, Florence | |
dc.creator.author | Pastor, Pau | |
dc.creator.author | Peters, Oliver | |
dc.creator.author | Pijnenburg, Yolande A L | |
dc.creator.author | Piñol-Ripoll, Gerard | |
dc.creator.author | Popp, Julius | |
dc.creator.author | Porcel, Laura Molina | |
dc.creator.author | Puerta, Raquel | |
dc.creator.author | Pérez-Tur, Jordi | |
dc.creator.author | Rainero, Innocenzo | |
dc.creator.author | Ramakers, Inez | |
dc.creator.author | Real, Luis M. | |
dc.creator.author | Riedel-Heller, Steffi | |
dc.creator.author | Rodriguez-Rodriguez, Eloy | |
dc.creator.author | Ross, Owen A. | |
dc.creator.author | Luís Royo, Jose | |
dc.creator.author | Rujescu, Dan | |
dc.creator.author | Scarmeas, Nikolaos | |
dc.creator.author | Scheltens, Philip | |
dc.creator.author | Scherbaum, Norbert | |
dc.creator.author | Schneider, Anja | |
dc.creator.author | Seripa, Davide | |
dc.creator.author | Skoog, Ingmar | |
dc.creator.author | Solfrizzi, Vincenzo | |
dc.creator.author | Spalletta, Gianfranco | |
dc.creator.author | Squassina, Alessio | |
dc.creator.author | van Swieten, John | |
dc.creator.author | Sánchez-Valle, Raquel | |
dc.creator.author | Tan, Eng-King | |
dc.creator.author | Tegos, Thomas | |
dc.creator.author | Teunissen, Charlotte | |
dc.creator.author | Thomassen, Jesper Qvist | |
dc.creator.author | Tremolizzo, Lucio | |
dc.creator.author | Vyhnalek, Martin | |
dc.creator.author | Verhey, Frans | |
dc.creator.author | Waern, Margda | |
dc.creator.author | Wiltfang, Jens | |
dc.creator.author | Zhang, Jing | |
dc.creator.author | Zetterberg, Henrik | |
dc.creator.author | Blennow, Kaj | |
dc.creator.author | He, Zihuai | |
dc.creator.author | Williams, Julie | |
dc.creator.author | Amouyel, Philippe | |
dc.creator.author | Jessen, Frank | |
dc.creator.author | Kehoe, Patrick G. | |
dc.creator.author | Andreassen, Ole | |
dc.creator.author | Van Duin, Cornelia | |
dc.creator.author | Tsolaki, Magda | |
dc.creator.author | Sánchez-Juan, Pascual | |
dc.creator.author | Frikke-Schmidt, Ruth | |
dc.creator.author | Sleegers, Kristel | |
dc.creator.author | Toda, Tatsushi | |
dc.creator.author | Zettergren, Anna | |
dc.creator.author | Ingelsson, Martin | |
dc.creator.author | Okada, Yukinori | |
dc.creator.author | Rossi, Giacomina | |
dc.creator.author | Hiltunen, Mikko | |
dc.creator.author | Gim, Jungsoo | |
dc.creator.author | Ozaki, Kouichi | |
dc.creator.author | Sims, Rebecca | |
dc.creator.author | Foo, Jia Nee | |
dc.creator.author | van der Flier, Wiesje | |
dc.creator.author | Ikeuchi, Takeshi | |
dc.creator.author | Ramirez, Alfredo | |
dc.creator.author | Mata, Ignacio | |
dc.creator.author | Ruiz, Agustín | |
dc.creator.author | Gan-Or, Ziv | |
dc.creator.author | Lambert, Jean-Charles | |
dc.creator.author | Greicius, Michael D. | |
dc.creator.author | Mignot, Emmanuel | |
cristin.unitcode | 185,53,10,70 | |
cristin.unitname | Senter for presisjonspsykiatri | |
cristin.ispublished | true | |
cristin.fulltext | original | |
cristin.qualitycode | 2 | |
dc.identifier.cristin | 2185961 | |
dc.identifier.bibliographiccitation | info:ofi/fmt:kev:mtx:ctx&ctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.jtitle=Proceedings of the National Academy of Sciences of the United States of America&rft.volume=120&rft.spage=&rft.date=2023 | |
dc.identifier.jtitle | Proceedings of the National Academy of Sciences of the United States of America | |
dc.identifier.volume | 120 | |
dc.identifier.issue | 36 | |
dc.identifier.pagecount | 0 | |
dc.identifier.doi | https://doi.org/10.1073/pnas.2302720120 | |
dc.type.document | Tidsskriftartikkel | |
dc.type.peerreviewed | Peer reviewed | |
dc.source.issn | 0027-8424 | |
dc.type.version | PublishedVersion | |
cristin.articleid | e2302720120 |
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