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

• Autores: van der Lee, Sven J.; Conway, Olivia J.; Jansen, Iris; Carrasquillo, Minerva M.; Kleineidam, Luca; van den Akker, Erik; Hernández, Isabel; van Eijk, Kristel R.; Stringa, Najada; Chen, Jason A.; Zettergren, Anna; Andlauer, Till F. M.; Diez Fairen, Monica; Simon Sanchez, Javier; Lleó, Alberto; Zetterberg, Henrik; Nygaard, Marianne; Blauwendraat, Cornelis; Savage, Jeanne E.; Mengel From, Jonas; Moreno Grau, Sonia; Wagner, Michael; Fortea, Juan; Keogh, Michael J.; Blennow, Kaj; Skoog, Ingmar; Friese, Manuel A.; Pletnikova, Olga; Zulaica, Miren; Dalmasso, Maria Carolina
• Año de publicación: 2019
• Idioma: inglés
• Tipo de recurso: artículo
• Materia: ALZHEIMER’S DISEASE; AMYOTROPHIC LATERAL SCLEROSIS; DEMENTIA WITH LEWY BODIES; FRONTOTEMPORAL DEMENTIA; LONGEVITY; MULTIPLE SCLEROSIS; NEURODEGENERATIVE DISEASE; PARKINSON’S DISEASE; PHOSPHOLIPASE C GAMMA 2; PLCG2; PROGRESSIVE SUPRANUCLEAR PALSY
• Institución: Consejo Nacional de Investigaciones Científicas y Técnicas

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.
Fil:  van der Lee, Sven J.. Vrije Universiteit Amsterdam; Países Bajos
Fil: Conway, Olivia J.. Mayo Clinic Cancer Center; Estados Unidos
Fil: Jansen, Iris. Vrije Universiteit Amsterdam; Países Bajos
Fil: Carrasquillo, Minerva M.. Mayo Clinic Cancer Center; Estados Unidos
Fil: Kleineidam, Luca. Universitat Bonn; Alemania. German Center for Neurodegenerative Diseases; Alemania. University Hospital Cologne; Alemania
Fil: van den Akker, Erik. Leiden University. Leiden University Medical Center; Países Bajos. Delft University of Technology; Países Bajos
Fil: Hernández, Isabel. Universitat Internacional de Catalunya; España. Centro de Investigacion Biomedica en Red en Enfermedades Neurodegenerativas ; España
Fil: van Eijk, Kristel R.. University of Utrecht; Países Bajos
Fil: Stringa, Najada. Vrije Universiteit Amsterdam; Países Bajos
Fil: Chen, Jason A.. University of California at Los Angeles; Estados Unidos
Fil: Zettergren, Anna. University of Gothenburg; Suecia
Fil: Andlauer, Till F. M.. Max Planck Institute of Psychiatry; Alemania. Universitat Technical Zu Munich; Alemania. German Competence Network Multiple Sclerosis; Alemania
Fil: Diez Fairen, Monica. University Hospital Mutua de Terrassa; España. Fundacio per la Recerca Biomedica I Social Mutua Terrassa; España
Fil: Simon Sanchez, Javier. Deutsches Zentrum für Neurodegenerative Erkrankungen; Alemania. Eberhard Karls Universität Tübingen; Alemania
Fil: Lleó, Alberto. Universitat Autònoma de Barcelona; España. Centro de Investigacion Biomedica en Red en Enfermedades Neurodegenerativas ; España
Fil: Zetterberg, Henrik. Sahlgrenska University Hospital; Suecia. University of Gothenburg; Suecia. University College London; Estados Unidos
Fil: Nygaard, Marianne. University of Southern Denmark; Dinamarca
Fil: Blauwendraat, Cornelis. National Institute of Neurological Disorders and Stroke; Estados Unidos
Fil: Savage, Jeanne E.. Vrije Universiteit Amsterdam; Países Bajos
Fil: Mengel From, Jonas. University of Southern Denmark; Dinamarca
Fil: Moreno Grau, Sonia. Universitat Internacional de Catalunya; España
Fil: Wagner, Michael. Universitat Bonn; Alemania. Deutsches Zentrum für Neurodegenerative Erkrankungen; Alemania
Fil: Fortea, Juan. Universitat Autònoma de Barcelona; España. Centro de Investigacion Biomedica en Red en Enfermedades Neurodegenerativas ; España
Fil: Keogh, Michael J.. University of Newcastle; Reino Unido. University of Cambridge; Reino Unido
Fil: Blennow, Kaj. Sahlgrenska University Hospital; Suecia. University of Gothenburg; Suecia
Fil: Skoog, Ingmar. University of Gothenburg; Suecia
Fil: Friese, Manuel A.. German Competence Network Multiple Sclerosis; Alemania. Universitätsklinikum Hamburg‐Eppendorf; Alemania
Fil: Pletnikova, Olga. University Johns Hopkins; Estados Unidos
Fil: Zulaica, Miren. Centro de Investigacion Biomedica en Red en Enfermedades Neurodegenerativas ; España. Instituto Biodonostia; España
Fil: Dalmasso, Maria Carolina. University Hospital Cologne; Alemania. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina