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Autor
Alvarez, Victoria 1 Ambati, Aditya 1 Amouyel, Philippe 1 Andreassen, Ole A 1 Arosio, Beatrice 1 Bellenguez, Céline 1 Belloy, Michael E 1 Benussi, Luisa 1 Blennow, Kaj 1 Boada, Mercè 1 Boland, Anne 1 Borroni, Barbara 1 Bullido, María J 1 Caffarra, Paolo 1 Clarimon, Jordi 1 Damotte, Vincent 1 Daniele, Antonio 1 Darling, Daniel 1 Debette, Stéphanie 1 Deleuze, Jean-François 1
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Pracoviště
1st Department of Neurology Aiginitio... 1 1st Department of Neurology Medical s... 1 Alzheimer Research Center and Memory ... 1 Alzheimer's Centre Reina Sofia CIEN F... 1 Alzheimer's disease and other cogniti... 1 Alzheimer's disease and other cogniti... 1 CHU de Bordeaux Pole santé publique B... 1 Center for Infectious Disease Educati... 1 Center for Sleep Sciences and Medicin... 1 Centre for Memory Disturbances Lab of... 1 Centro de Biología Molecular Severo O... 1 Charité Universitätsmedizin Berlin Co... 1 Charité Universitätsmedizin Berlin Ei... 1 Clinic of Neurology UH Alexandrovska ... 1 Clinical Neurochemistry Laboratory Sa... 1 Cluster of Excellence Cellular Stress... 1 Complex Genetics of Alzheimer's Disea... 1 Department for Neurodegenerative Dise... 1 Department of Biomedical Science Chos... 1 Department of Biomedical Science Chos... 1
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Autor
Alvarez, Victoria 1 Ambati, Aditya 1 Amouyel, Philippe 1 Andreassen, Ole A 1 Arosio, Beatrice 1 Bellenguez, Céline 1 Belloy, Michael E 1 Benussi, Luisa 1 Blennow, Kaj 1 Boada, Mercè 1 Boland, Anne 1 Borroni, Barbara 1 Bullido, María J 1 Caffarra, Paolo 1 Clarimon, Jordi 1 Damotte, Vincent 1 Daniele, Antonio 1 Darling, Daniel 1 Debette, Stéphanie 1 Deleuze, Jean-François 1
- Organizace
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Pracoviště
1st Department of Neurology Aiginitio... 1 1st Department of Neurology Medical s... 1 Alzheimer Research Center and Memory ... 1 Alzheimer's Centre Reina Sofia CIEN F... 1 Alzheimer's disease and other cogniti... 1 Alzheimer's disease and other cogniti... 1 CHU de Bordeaux Pole santé publique B... 1 Center for Infectious Disease Educati... 1 Center for Sleep Sciences and Medicin... 1 Centre for Memory Disturbances Lab of... 1 Centro de Biología Molecular Severo O... 1 Charité Universitätsmedizin Berlin Co... 1 Charité Universitätsmedizin Berlin Ei... 1 Clinic of Neurology UH Alexandrovska ... 1 Clinical Neurochemistry Laboratory Sa... 1 Cluster of Excellence Cellular Stress... 1 Complex Genetics of Alzheimer's Disea... 1 Department for Neurodegenerative Dise... 1 Department of Biomedical Science Chos... 1 Department of Biomedical Science Chos... 1
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- Le Guen, Yann
- Luo, Guo
- Ambati, Aditya
- Damotte, Vincent
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Jansen, Iris
Autor Jansen, Iris Department of Neurology, Alzheimer Center Amsterdam, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam UMC, 1081 HV Amsterdam, The Netherlands Department of Complex Trait Genetics, Center for Neurogenomics and Cognitive Research, Amsterdam Neuroscience, Vrije University, 1081 HV Amsterdam, The Netherlands
- Yu, Eric
- Nicolas, Aude
- de Rojas, Itziar
- Peixoto Leal, Thiago
- Miyashita, Akinori
Freely Accessible Science Journals od 1915 do Před 6 měsíci
PubMed Central od 1915 do Před 6 měsíci
Europe PubMed Central od 1915 do Před 6 měsíci
Open Access Digital Library od 1915-01-15
Open Access Digital Library od 1915-01-01
PubMed
37643212
DOI
10.1073/pnas.2302720120
Knihovny.cz E-zdroje
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.
- MeSH
- Alzheimerova nemoc * genetika MeSH
- histokompatibilita - antigeny MeSH
- HLA antigeny MeSH
- HLA-DRB1 řetězec * genetika MeSH
- lidé MeSH
- Parkinsonova nemoc * genetika MeSH
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- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, N.I.H., Extramural MeSH
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