التفاصيل البيبلوغرافية
العنوان: |
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. |
المؤلفون: |
Le Guen, Yann, Luo, Guo, Bellenguez, Céline, Sánchez-Valle, Raquel, Tan, Eng-King, Tegos, Thomas, Teunissen, Charlotte, Thomassen, Jesper Qvist, Tremolizzo, Lucio, Vyhnalek, Martin, Verhey, Frans, Waern, Margda, Wiltfang, Jens, Lian, Michelle Mulan, Zhang, Jing, EADB, group, GR@ACE study, consortium, DEGESCO, DemGene, EADI, GERAD, consortium, Asian Parkinson’s Disease Genetics, Zetterberg, Henrik, Blennow, Kaj, Parveen, Kayenat, He, Zihuai, Williams, Julie, Amouyel, Philippe, Jessen, Frank, Kehoe, Patrick G, Andreassen, Ole A, Van Duin, Cornelia, Tsolaki, Magda, Sánchez-Juan, Pascual, Frikke-Schmidt, Ruth, Morizono, Takashi, Sleegers, Kristel, Toda, Tatsushi, Zettergren, Anna, Ingelsson, Martin, Okada, Yukinori, Rossi, Giacomina, Hiltunen, Mikko, Gim, Jungsoo, Ozaki, Kouichi, Sims, Rebecca, Park, Hyeonseul, 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, Grenier-Boley, Benjamin, Naito, Tatsuhiko, Küçükali, Fahri, Talyansky, Seth D, Yogeshwar, Selina Maria, Ambati, Aditya, Sempere, Vicente, Satake, Wataru, Alvarez, Victoria, Arosio, Beatrice, Belloy, Michael E, Benussi, Luisa, Boland, Anne, Borroni, Barbara, Bullido, María J, Caffarra, Paolo, Damotte, Vincent, Clarimon, Jordi, Daniele, Antonio, Darling, Daniel, Debette, Stéphanie, Deleuze, Jean-François, Dichgans, Martin, Dufouil, Carole, During, Emmanuel, Düzel, Emrah, Galimberti, Daniela, Jansen, Iris, 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, Yu, Eric, Holstege, Henne, Hort, Jakub, Jung, Yoo Jin, Jürgen, Deckert, Kern, Silke, Kuulasmaa, Teemu, Lee, Kun Ho, Lin, Ling, Masullo, Carlo, Mecocci, Patrizia, Nicolas, Aude, Mehrabian, Shima, de Mendonça, Alexandre, Boada, Mercè, Mir, Pablo, Moebus, Susanne, Moreno, Fermin, Nacmias, Benedetta, Nicolas, Gael, Niida, Shumpei, Nordestgaard, Børge G, de Rojas, Itziar, Papenberg, Goran, Papma, Janne, Parnetti, Lucilla, Pasquier, Florence, Pastor, Pau, Peters, Oliver, Pijnenburg, Yolande A L, Piñol-Ripoll, Gerard, Popp, Julius, Porcel, Laura Molina, Peixoto Leal, Thiago, 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, Miyashita, Akinori, Scarmeas, Nikolaos, Scheltens, Philip, Scherbaum, Norbert, Schneider, Anja, Seripa, Davide, Skoog, Ingmar, Solfrizzi, Vincenzo, Spalletta, Gianfranco, Squassina, Alessio, van Swieten, John |
المصدر: |
Proceedings of the National Academy of Sciences of the United States of America 120(36), e2302720120 (2023). doi:10.1073/pnas.2302720120 |
بيانات النشر: |
National Acad. of Sciences |
سنة النشر: |
2023 |
مصطلحات موضوعية: |
info:eu-repo/classification/ddc/500, Humans, Alzheimer Disease: genetics, Histocompatibility Antigens, HLA Antigens, HLA-DRB1 Chains: genetics, Parkinson Disease: genetics, Alzheimer’s dementia, HLA, Parkinson’s disease, autoimmunity, neurodegeneration, HLA-DRB1 Chains, HLA-DRB1*04 antigen |
جغرافية الموضوع: |
DE |
الوصف: |
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. |
نوع الوثيقة: |
article in journal/newspaper |
اللغة: |
English |
العلاقة: |
info:eu-repo/semantics/altIdentifier/issn/0027-8424; info:eu-repo/semantics/altIdentifier/issn/1091-6490; info:eu-repo/semantics/altIdentifier/pmid/pmid:37643212; https://pub.dzne.de/record/263618Test; https://pub.dzne.de/search?p=id:%22DZNE-2023-00840%22Test |
الإتاحة: |
https://doi.org/10.1073/pnas.2302720120Test https://pub.dzne.de/record/263618Test https://pub.dzne.de/search?p=id:%22DZNE-2023-00840%22Test |
حقوق: |
info:eu-repo/semantics/openAccess |
رقم الانضمام: |
edsbas.2ECE453 |
قاعدة البيانات: |
BASE |