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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.rights.licenseopenen_US
dc.contributor.authorLE GUEN, Yann
dc.contributor.authorLUO, Guo
dc.contributor.authorAMBATI, Aditya
dc.contributor.authorDAMOTTE, Vincent
dc.contributor.authorJANSEN, Iris
dc.contributor.authorYU, Eric
dc.contributor.authorNICOLAS, Aude
dc.contributor.authorDE ROJAS, Itziar
dc.contributor.authorPEIXOTO LEAL, Thiago
dc.contributor.authorMIYASHITA, Akinori
dc.contributor.authorBELLENGUEZ, Celine
dc.contributor.authorLIAN, Michelle Mulan
dc.contributor.authorPARVEEN, Kayenat
dc.contributor.authorMORIZONO, Takashi
dc.contributor.authorPARK, Hyeonseul
dc.contributor.authorGRENIER-BOLEY, Benjamin
dc.contributor.authorNAITO, Tatsuhiko
dc.contributor.authorKUCUKALI, Fahri
dc.contributor.authorTALYANSKY, Seth D
dc.contributor.authorYOGESHWAR, Selina Maria
dc.contributor.authorSEMPERE, Vicente
dc.contributor.authorSATAKE, Wataru
dc.contributor.authorALVAREZ, Victoria
dc.contributor.authorAROSIO, Beatrice
dc.contributor.authorBELLOY, Michael E
dc.contributor.authorBENUSSI, Luisa
dc.contributor.authorBOLAND, Anne
dc.contributor.authorBORRONI, Barbara
dc.contributor.authorBULLIDO, Maria J
dc.contributor.authorCAFFARRA, Paolo
dc.contributor.authorCLARIMON, Jordi
dc.contributor.authorDANIELE, Antonio
dc.contributor.authorDARLING, Daniel
hal.structure.identifierBordeaux population health [BPH]
dc.contributor.authorDEBETTE, Stephanie
dc.contributor.authorDELEUZE, Jean-Francois
dc.contributor.authorDICHGANS, Martin
hal.structure.identifierBordeaux population health [BPH]
dc.contributor.authorDUFOUIL, Carole
dc.contributor.authorDURING, Emmanuel
dc.contributor.authorDUZEL, Emrah
dc.contributor.authorGALIMBERTI, Daniela
dc.contributor.authorGARCIA-RIBAS, Guillermo
dc.contributor.authorGARCIA-ALBERCA, Jose Maria
dc.contributor.authorGARCIA-GONZALEZ, Pablo
dc.contributor.authorGIEDRAITIS, Vilmantas
dc.contributor.authorGOLDHARDT, Oliver
dc.contributor.authorGRAFF, Caroline
dc.contributor.authorGRUNBLATT, Edna
dc.contributor.authorHANON, Olivier
dc.contributor.authorHAUSNER, Lucrezia
dc.contributor.authorHEILMANN-HEIMBACH, Stefanie
dc.contributor.authorHOLSTEGE, Henne
dc.contributor.authorHORT, Jakub
dc.contributor.authorJUNG, Yoo Jin
dc.contributor.authorJURGEN, Deckert
dc.contributor.authorKERN, Silke
dc.contributor.authorKUULASMAA, Teemu
dc.contributor.authorLEE, Kun Ho
dc.contributor.authorLIN, Ling
dc.contributor.authorMASULLO, Carlo
dc.contributor.authorMECOCCI, Patrizia
dc.contributor.authorMEHRABIAN, Shima
dc.contributor.authorDE MENDONCA, Alexandre
dc.contributor.authorBOADA, Merce
dc.contributor.authorMIR, Pablo
dc.contributor.authorMOEBUS, Susanne
dc.contributor.authorMORENO, Fermin
dc.contributor.authorNACMIAS, Benedetta
dc.contributor.authorNICOLAS, Gael
dc.contributor.authorNIIDA, Shumpei
dc.contributor.authorNORDESTGAARD, Borge G
dc.contributor.authorPAPENBERG, Goran
dc.contributor.authorPAPMA, Janne
dc.contributor.authorPARNETTI, Lucilla
dc.contributor.authorPASQUIER, Florence
dc.contributor.authorPASTOR, Pau
dc.contributor.authorPETERS, Oliver
dc.contributor.authorPIJNENBURG, Yolande A L
dc.contributor.authorPINOL-RIPOLL, Gerard
dc.contributor.authorPOPP, Julius
dc.contributor.authorPORCEL, Laura Molina
dc.contributor.authorPUERTA, Raquel
dc.contributor.authorPEREZ-TUR, Jordi
dc.contributor.authorRAINERO, Innocenzo
dc.contributor.authorRAMAKERS, Inez
dc.contributor.authorREAL, Luis M
dc.contributor.authorRIEDEL-HELLER, Steffi
dc.contributor.authorRODRIGUEZ-RODRIGUEZ, Eloy
dc.contributor.authorROSS, Owen A
dc.contributor.authorROYO, Luis Jose
dc.contributor.authorRUJESCU, Dan
dc.contributor.authorSCARMEAS, Nikolaos
dc.contributor.authorSCHELTENS, Philip
dc.contributor.authorSCHERBAUM, Norbert
dc.contributor.authorSCHNEIDER, Anja
dc.contributor.authorSERIPA, Davide
dc.contributor.authorSKOOG, Ingmar
dc.contributor.authorSOLFRIZZI, Vincenzo
dc.contributor.authorSPALLETTA, Gianfranco
dc.contributor.authorSQUASSINA, Alessio
dc.contributor.authorVAN SWIETEN, John
dc.contributor.authorSANCHEZ-VALLE, Raquel
dc.contributor.authorTAN, Eng-King
dc.contributor.authorTEGOS, Thomas
dc.contributor.authorTEUNISSEN, Charlotte
dc.contributor.authorTHOMASSEN, Jesper Qvist
dc.contributor.authorTREMOLIZZO, Lucio
dc.contributor.authorVYHNALEK, Martin
dc.contributor.authorVERHEY, Frans
dc.contributor.authorWAERN, Margda
dc.contributor.authorWILTFANG, Jens
dc.contributor.authorZHANG, Jing
dc.contributor.authorZETTERBERG, Henrik
dc.contributor.authorBLENNOW, Kaj
dc.contributor.authorHE, Zihuai
dc.contributor.authorWILLIAMS, Julie
dc.contributor.authorAMOUYEL, Philippe
dc.contributor.authorJESSEN, Frank
dc.contributor.authorKEHOE, Patrick G
dc.contributor.authorANDREASSEN, Ole A
dc.contributor.authorVAN DUIN, Cornelia
dc.contributor.authorTSOLAKI, Magda
dc.contributor.authorSANCHEZ-JUAN, Pascual
dc.contributor.authorFRIKKE-SCHMIDT, Ruth
dc.contributor.authorSLEEGERS, Kristel
dc.contributor.authorTODA, Tatsushi
dc.contributor.authorZETTERGREN, Anna
dc.contributor.authorINGELSSON, Martin
dc.contributor.authorOKADA, Yukinori
dc.contributor.authorROSSI, Giacomina
dc.contributor.authorHILTUNEN, Mikko
dc.contributor.authorGIM, Jungsoo
dc.contributor.authorOZAKI, Kouichi
dc.contributor.authorSIMS, Rebecca
dc.contributor.authorFOO, Jia Nee
dc.contributor.authorVAN DER FLIER, Wiesje
dc.contributor.authorIKEUCHI, Takeshi
dc.contributor.authorRAMIREZ, Alfredo
dc.contributor.authorMATA, Ignacio
dc.contributor.authorRUIZ, Agustin
dc.contributor.authorGAN-OR, Ziv
dc.contributor.authorLAMBERT, Jean-Charles
dc.contributor.authorGREICIUS, Michael D
dc.contributor.authorMIGNOT, Emmanuel
dc.date.accessioned2024-05-22T08:11:34Z
dc.date.available2024-05-22T08:11:34Z
dc.date.issued2023-09-05
dc.identifier.issn1091-6490en_US
dc.identifier.urihttps://oskar-bordeaux.fr/handle/20.500.12278/199971
dc.description.abstractEnAcross 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 A beta 42. 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.isoENen_US
dc.rightsAttribution 3.0 United States*
dc.rights.urihttp://creativecommons.org/licenses/by/3.0/us/*
dc.subject.enAlzheimer’s Dementia
dc.subject.enHLA
dc.subject.enParkinson’s Disease
dc.subject.enAutoimmunity
dc.subject.enNeurodegeneration
dc.title.enMultiancestry 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.alternativeProc Natl Acad Sci U S A
dc.typeArticle de revueen_US
dc.identifier.doi10.1073/pnas.2302720120en_US
dc.subject.halSciences du Vivant [q-bio]/Santé publique et épidémiologieen_US
dc.identifier.pubmed37643212en_US
bordeaux.journalProceedings of the National Academy of Sciences of the United States of Americaen_US
bordeaux.pagee2302720120en_US
bordeaux.volume120en_US
bordeaux.hal.laboratoriesBordeaux Population Health Research Center (BPH) - UMR 1219en_US
bordeaux.issue36en_US
bordeaux.institutionUniversité de Bordeauxen_US
bordeaux.institutionINSERMen_US
bordeaux.teamELEANOR_BPHen_US
bordeaux.teamPHARES_BPHen_US
bordeaux.peerReviewedouien_US
bordeaux.inpressnonen_US
bordeaux.identifier.funderIDHorizon 2020en_US
bordeaux.identifier.funderIDAlzheimer's Associationen_US
bordeaux.identifier.funderIDNational Institutes of Healthen_US
hal.popularnonen_US
hal.audienceInternationaleen_US
hal.exportfalse
dc.rights.ccPas de Licence CCen_US
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