A nonsynonymous mutation in PLCG2 reduces the risk of Alzheimer's disease, dementia with Lewy bodies and frontotemporal dementia, and increases the likelihood of longevity
van der Lee, Sven J. (Vrije Universiteit Amsterdam, Amsterdam UMC. Department of Clinical Genetics)
Conway, Olivia J. (Mayo Clinic Florida. Department of Neuroscience)
Jansen, Iris E (Vrije Universiteit Amsterdam, Amsterdam UMC. Department of Complex Trait Genetics, Center for Neurogenomics and Cognitive Research, Amsterdam Neuroscience)
Carrasquillo, Minerva M. (Mayo Clinic Florida. Department of Neuroscience)
Kleineidam, Luca (Uniklinik Köln (Colònia, Alemanya))
van den Akker, Erik (Delft University of Technology. Pattern Recognition and Bioinformatics)
Hernández, Isabel (Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas)
van Eijk, Kristel R. (University Medical Center Utrecht. Department of Neurology, Brain Center Rudolf Magnus)
Stringa, Najada (Vrije Universiteit Amsterdam)
Chen, Jason A. (University of California. Interdepartmental Program in Bioinformatics)
Zettergren, Anna (Neuropsychiatric Epidemiology Unit, Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy, Centre for Ageing and Health (AgeCap) at the University of Gothenburg)
Andlauer, Till F. M. (German Competence Network Multiple Sclerosis (KKNMS))
Diez-Fairen, Monica (Fundacio per la Recerca Biomedica I Social Mutua Terrassa)
Simon-Sanchez, Javier (University of Tübingen. Hertie Institute for Clinical Brain Research)
Lleó, Alberto (Institut d'Investigació Biomèdica Sant Pau)
Zetterberg, Henrik (UCL Institute of Neurology (Regne Unit). Department of Molecular Neuroscience)
Nygaard, Marianne (University of Southern Denmark. The Danish Aging Research Center, Epidemiology, Biostatistics and Biodemography, Department of Public Health)
Blauwendraat, Cornelis (National Institute of Neurological Disorders and Stroke. Neurodegenerative Diseases Research Unit)
Savage, Jeanne E. (Vrije Universiteit Amsterdam, Amsterdam UMC. Department of Complex Trait Genetics, Center for Neurogenomics and Cognitive Research, Amsterdam Neuroscience)
Mengel-From, Jonas (University of Southern Denmark. Epidemiology, Biostatistics and Biodemography, Department of Public Health)
Moreno-Grau, Sonia (Institut Català de Neurociènces Aplicades)
Wagner, Michael (DZNE, German Center for Neurodegenerative Diseases)
Fortea, Juan (Institut d'Investigació Biomèdica Sant Pau)
Keogh, Michael J. (University of Cambridge. Department of Clinical Neurosciences)
Blennow, Kaj (Institute of Neuroscience and Physiology, Sahlgrenska Academy at the University of Gothenburg. Department of Psychiatry and Neurochemistry)
Skoog, Ingmar (Neuropsychiatric Epidemiology Unit, Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy, Centre for Ageing and Health (AgeCap) at the University of Gothenburg)
Friese, Manuel A. (Universitätsklinikum Hamburg-Eppendorf. Institut für Neuroimmunologie und Multiple Sklerose (INIMS))
Pletnikova, Olga (Johns Hopkins University Medical Center. Department of Pathology (Neuropathology))
Zulaica, Miren (Biodonostia Osasun Ikerketako Institutura (País Basc))
Lage, Carmen (IDIVAL)
De Rojas, Itziar (Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas)
Riedel-Heller, Steffi (University of Leipzig. Institute of Social Medicine, Occupational Health and Public Health (ISAP))
Illán-Gala, Ignacio (Institut d'Investigació Biomèdica Sant Pau)
Wei, Wei (University of Cambridge. Department of Clinical Neurosciences)
Jeune, Bernard (University of Southern Denmark. Epidemiology, Biostatistics and Biodemography, Department of Public Health)
Orellana, Adelina (Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas)
Then Bergh, Florian (University of Leipzig. Department of Neurology)
Wang, Xue (Mayo Clinic Florida. Department of Neuroscience)
Hulsman, Marc (Delft University of Technology. Pattern Recognition and Bioinformatics)
Beker, Nina (Vrije Universiteit Amsterdam, Amsterdam UMC. Alzheimer Center Amsterdam, Department of Neurology, Amsterdam Neuroscience)
Tesi, Niccolo (Delft University of Technology. Pattern Recognition and Bioinformatics)
Morris, Christopher M. (Newcastle University. Newcastle Brain Tissue Resource, Edwardson Building, Institute of Neuroscience)
Indakoetxea, Begoña (Hospital Universitario de Donostia (Sant Sebastià, País Basc))
Collij, Lyduine E. (Vrije Universiteit Amsterdam, Amsterdam UMC. Department of Radiology and Nuclear Medicine, Amsterdam Neuroscience)
Scherer, Martin (Department of Primary Medical Care, Center for Psychosocial Medicine, University Medical Center, Hamburg-Eppendorf, Germany)
Morenas-Rodríguez, Estrella (Institut d'Investigació Biomèdica Sant Pau)
Ironside, James W. (University of Edinburgh. Centre for Clinical Brain Sciences)
van Berckel, Bart N. M. (Vrije Universiteit Amsterdam, Amsterdam UMC. Department of Radiology and Nuclear Medicine, Amsterdam Neuroscience)
Alcolea, Daniel (Institut d'Investigació Biomèdica Sant Pau)
Wiendl, Heinz (University of Münster. Department of Neurology, Klinik für Neurologie mit Institut für Translationale Neurologie)
Strickland, Samantha L. (Mayo Clinic Florida. Department of Neuroscience)
Pastor, Pau (Fundacio per la Recerca Biomedica I Social Mutua Terrassa)
Rodríguez-Rodríguez, Eloy (IDIVAL)
Boeve, Bradley (Mayo Clinic Minnesota. Department of Neurology)
Petersen, Ronald C. (Mayo Clinic Minnesota. Department of Neurology)
Ferman, Tanis J. (Mayo Clinic Florida. Department of Psychiatry and Psychology)
van Gerpen, Jay A. (Mayo Clinic Florida. Department of Neurology)
Reinders, Marcel J. T. (Delft University of Technology. Delft Bioinformatics Lab)
Uitti, Ryan J. (Mayo Clinic Florida. Department of Neurology)
Tárraga, Lluís (Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas)
Maier, Wolfgang (DZNE, German Center for Neurodegenerative Diseases)
Dols Icardo, Oriol (Institut d'Investigació Biomèdica Sant Pau)
Kawalia, Amit (Uniklinik Köln (Colònia, Alemanya))
Dalmasso, Maria Carolina (Fundación Instituto Leloir (Buenos Aires, Argentina))
Boada, Mercè (Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas)
Zettl, Uwe K. (University of Rostock. Department of Neurology)
van Schoor, Natasja M. (Vrije Universiteit Amsterdam)
Beekman, Marian (Leiden University Medical Center. Molecular Epidemiology)
Allen, Mariet (Mayo Clinic Florida. Department of Neuroscience)
Masliah, Eliezer (National Institute on Aging (Estats Units d'Amèrica))
de Munain, Adolfo López (Department of Neurology, Hospital Universitario San Sebastian, San Sebastian, Spain)
Pantelyat, Alexander (Johns Hopkins University Medical Center. Department of Neurology)
Wszolek, Zbigniew K. (Mayo Clinic Florida. Department of Neurology)
Ross, Owen A. (Mayo Clinic Florida. Department of Neuroscience)
Dickson, Dennis W. (Mayo Clinic Florida. Department of Neuroscience)
Graff-Radford, Neill R. (Mayo Clinic Florida. Department of Neurology)
Knopman, David (Mayo Clinic Minnesota. Department of Neurology)
Rademakers, Rosa (Mayo Clinic Florida. Department of Neuroscience)
Lemstra, Afina W. (Vrije Universiteit Amsterdam, Amsterdam UMC. Alzheimer Center Amsterdam, Department of Neurology, Amsterdam Neuroscience)
Pijnenburg, Yolande (Vrije Universiteit Amsterdam, Amsterdam UMC. Alzheimer Center Amsterdam, Department of Neurology, Amsterdam Neuroscience)
Scheltens, Philip (Vrije Universiteit Amsterdam, Amsterdam UMC. Alzheimer Center Amsterdam, Department of Neurology, Amsterdam Neuroscience)
Gasser, Thomas (University of Tuebingen. Center of Neurology, Department of Neurodegenerative diseases, Hertie-Institute for Clinical Brain Research)
Chinnery, Patrick F. (University of Cambridge. MRC Mitochondrial Biology Unit)
Hemmer, Bernhard (Munich Cluster for Systems Neurology (SyNergy))
Huisman, Martijn A. (VU University. Department of Sociology)
Troncoso, Juan (Johns Hopkins University Medical Center. Department of Pathology (Neuropathology))
Moreno, Fermin (Hospital Universitario de Donostia (Sant Sebastià, País Basc))
Nohr, Ellen A. (University of Southern Denmark. Research Unit of Gynecology and Obstetrics, Department of Clinical Research)
Sørensen, Thorkild I. A. (Bristol University. MRC Integrative Epidemiology Unit)
Heutink, Peter (University of Tübingen. Hertie Institute for Clinical Brain Research)
Sánchez-Juan, Pascual (IDIVAL)
Posthuma, Danielle (Vrije Universiteit Amsterdam, Amsterdam UMC. Department of Complex Trait Genetics, Center for Neurogenomics and Cognitive Research, Amsterdam Neuroscience)
Clarimón, Jordi (Institut d'Investigació Biomèdica Sant Pau)
Christensen, Kaare (Odense University Hospital (Dinamarca))
Ertekin-Taner, Nilüfer (Mayo Clinic Florida. Department of Neurology)
Scholz, Sonja (Johns Hopkins University Medical Center. Department of Neurology)
Ramirez, Alfredo (Uniklinik Köln (Colònia, Alemanya))
Ruiz, Agustín (Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas)
Slagboom, Eline (Dutch Society for Research on Ageing, Leiden, The Netherlands)
van der Flier, Wiesje M. (Vrije Universiteit Amsterdam, Amsterdam UMC. Alzheimer Center Amsterdam, Department of Neurology, Amsterdam Neuroscience)
Holstege, Henne (Vrije Universiteit Amsterdam, Amsterdam UMC. Department of Clinical Genetics)
Universitat Autònoma de Barcelona

Data:	2019
Resum:	The genetic variant rs72824905-G (minor allele) in the PLCG2 gene was previously associated with a reduced Alzheimer's disease risk (AD). The role of PLCG2 in immune system signaling suggests it may also protect against other neurodegenerative diseases and possibly associates with longevity. We studied the effect of the rs72824905-G on seven neurodegenerative diseases and longevity, using 53,627 patients, 3,516 long-lived individuals and 149,290 study-matched controls. We replicated the association of rs72824905-G with reduced AD risk and we found an association with reduced risk of dementia with Lewy bodies (DLB) and frontotemporal dementia (FTD). We did not find evidence for an effect on Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS) and multiple sclerosis (MS) risks, despite adequate sample sizes. Conversely, the rs72824905-G allele was associated with increased likelihood of longevity. By-proxy analyses in the UK Biobank supported the associations with both dementia and longevity. Concluding, rs72824905-G has a protective effect against multiple neurodegenerative diseases indicating shared aspects of disease etiology. Our findings merit studying the PLCγ2 pathway as drug-target.
Ajuts:	Instituto de Salud Carlos III PI08-0139 Instituto de Salud Carlos III PI12-02288 Instituto de Salud Carlos III PI16-01652 Agència de Gestió d'Ajuts Universitaris i de Recerca 2017 SGR 547 Instituto de Salud Carlos III PI11-02526 Instituto de Salud Carlos III PI14-01126 Instituto de Salud Carlos III PI17-01019 Instituto de Salud Carlos III PI17-01895
Nota:	The online version of this article (10.1007/s00401-019-02026-8) contains supplementary material, which is available to authorized users.
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	Alzheimer's disease ; Frontotemporal dementia ; Dementia with Lewy bodies ; Progressive supranuclear palsy ; Parkinson's disease ; Amyotrophic lateral sclerosis ; Multiple sclerosis ; Neurodegenerative disease ; Longevity ; PLCG2 ; Phospholipase C Gamma 2
Publicat a:	Acta Neuropathologica, Vol. 138 (may 2019) , p. 237-250, ISSN 1432-0533
Obra relacionada:	van der Lee, S.J., Conway, O.J., Jansen, I. [et al.] "Correction to: A nonsynonymous mutation in PLCG2 reduces the risk of Alzheimer's disease, dementia with Lewy bodies and frontotemporal dementia, and increases the likelihood of longevity". Acta Neuropathologica, vol. 139, p. 959-962 (2020) https://doi.org/10.1007/s00401-019-02107-8

Correcció: https://ddd.uab.cat/record/226203
DOI: 10.1007/s00401-019-02026-8
PMID: 31131421

14 p, 1.2 MB

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