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, SJ; Conway, OJ; Jansen, I; Carrasquillo, MM; Kleineidam, L; van den Akker, E; Hernandez, I; van Eijk, KR; Stringa, N; Chen, JA; Zettergren, A; Andlauer, TFM; Diez-Fairen, M; Simon-Sanchez, J; Lleo, A; Zetterberg, H; Nygaard, M; Blauwendraat, C; Savage, JE; Mengel-From, J; Moreno-Grau, S; Wagner, M; Fortea, J; Keogh, MJ; Blennow, K; Skoog, I; Friese, MA; Pletnikova, O; Zulaica, M; Lage, C; de Rojas, I; Riedel-Heller, S; Illan-Gala, I; Wei, W; Jeune, B; Orellana, A; Bergh, FT; Wang, X; Hulsman, M; Beker, N; Tesi, N; Morris, CM; Indakoetxea, B; Collij, LE; Scherer, M; Morenas-Rodriguez, E; Ironside, JW; van Berckel, BNM; Alcolea, D; Wiendl, H; Strickland, SL; Pastor, P; Rodriguez Rodriguez, E; Boeve, BF; Petersen, RC; Ferman, TJ; van Gerpen, JA; Reinders, MJT; Uitti, RJ; Tarraga, L; Maier, W; Dols-Icardo, O; Kawalia, A; Dalmasso, MC; Boada, M; Zettl, UK; van Schoor, NM; Beekman, M; Allen, M; Masliah, E; de Munain, AL; Pantelyat, A; Wszolek, ZK; Ross, OA; Dickson, DW; Graff-Radford, NR; Knopman, D; Rademakers, R; Lemstra, AW; Pijnenburg, YAL; Scheltens, P; Gasser, T; Chinnery, PF; Hemmer, B; Huisman, MA; Troncoso, J; Moreno, F; Nohr, EA; Sorensen, TIA; Heutink, P; Sanchez-Juan, P; Posthuma, D; Clarimon, J; Christensen, K; Ertekin-Taner, N; Scholz, SW; Ramirez, A; Ruiz, A; Slagboom, E; van der Flier, WM; Holstege, H

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

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...

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Autores:	van der Lee, SJ, Conway, OJ, Jansen, I, Carrasquillo, MM, Kleineidam, L, van den Akker, E, Hernandez, I, van Eijk, KR, Stringa, N, Chen, JA, Zettergren, A, Andlauer, TFM, Diez-Fairen, M, Simon-Sanchez, J, Lleo, A, Zetterberg, H, Nygaard, M, Blauwendraat, C, Savage, JE, Mengel-From, J, Moreno-Grau, S, Wagner, M, Fortea, J, Keogh, MJ, Blennow, K, Skoog, I, Friese, MA, Pletnikova, O, Zulaica, M, Lage, C, de Rojas, I, Riedel-Heller, S, Illan-Gala, I, Wei, W, Jeune, B, Orellana, A, Bergh, FT, Wang, X, Hulsman, M, Beker, N, Tesi, N, Morris, CM, Indakoetxea, B, Collij, LE, Scherer, M, Morenas-Rodriguez, E, Ironside, JW, van Berckel, BNM, Alcolea, D, Wiendl, H, Strickland, SL, Pastor, P, Rodriguez Rodriguez, E, Boeve, BF, Petersen, RC, Ferman, TJ, van Gerpen, JA, Reinders, MJT, Uitti, RJ, Tarraga, L, Maier, W, Dols-Icardo, O, Kawalia, A, Dalmasso, MC, Boada, M, Zettl, UK, van Schoor, NM, Beekman, M, Allen, M, Masliah, E, de Munain, AL, Pantelyat, A, Wszolek, ZK, Ross, OA, Dickson, DW, Graff-Radford, NR, Knopman, D, Rademakers, R, Lemstra, AW, Pijnenburg, YAL, Scheltens, P, Gasser, T, Chinnery, PF, Hemmer, B, Huisman, MA, Troncoso, J, Moreno, F, Nohr, EA, Sorensen, TIA, Heutink, P, Sanchez-Juan, P, Posthuma, D, Clarimon, J, Christensen, K, Ertekin-Taner, N, Scholz, SW, Ramirez, A, Ruiz, A, Slagboom, E, van der Flier, WM, Holstege, H
Formato:	artículo
Estado:	Versión publicada
Fecha de publicación:	2019
País:	España
Recursos:	Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau)
Repositorio:	r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau
OAI Identifier:	oai:iibsantpau.fundanetsuite.com:p2515
Acesso em linha:	https://iibsantpau.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=2515 http://ddd.uab.cat/record/226469
Access Level:	acceso abierto
Palavra-chave:	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

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repository_id_str
spelling	A nonsynonymous mutation in PLCG2 reduces the risk of Alzheimer's disease, dementia with Lewy bodies and frontotemporal dementia, and increases the likelihood of longevityvan der Lee, SJConway, OJJansen, ICarrasquillo, MMKleineidam, Lvan den Akker, EHernandez, Ivan Eijk, KRStringa, NChen, JAZettergren, AAndlauer, TFMDiez-Fairen, MSimon-Sanchez, JLleo, AZetterberg, HNygaard, MBlauwendraat, CSavage, JEMengel-From, JMoreno-Grau, SWagner, MFortea, JKeogh, MJBlennow, KSkoog, IFriese, MAPletnikova, OZulaica, MLage, Cde Rojas, IRiedel-Heller, SIllan-Gala, IWei, WJeune, BOrellana, ABergh, FTWang, XHulsman, MBeker, NTesi, NMorris, CMIndakoetxea, BCollij, LEScherer, MMorenas-Rodriguez, EIronside, JWvan Berckel, BNMAlcolea, DWiendl, HStrickland, SLPastor, PRodriguez Rodriguez, EBoeve, BFPetersen, RCFerman, TJvan Gerpen, JAReinders, MJTUitti, RJTarraga, LMaier, WDols-Icardo, OKawalia, ADalmasso, MCBoada, MZettl, UKvan Schoor, NMBeekman, MAllen, MMasliah, Ede Munain, ALPantelyat, AWszolek, ZKRoss, OADickson, DWGraff-Radford, NRKnopman, DRademakers, RLemstra, AWPijnenburg, YALScheltens, PGasser, TChinnery, PFHemmer, BHuisman, MATroncoso, JMoreno, FNohr, EASorensen, TIAHeutink, PSanchez-Juan, PPosthuma, DClarimon, JChristensen, KErtekin-Taner, NScholz, SWRamirez, ARuiz, ASlagboom, Evan der Flier, WMHolstege, HAlzheimer's diseaseFrontotemporal dementiaDementia with Lewy bodiesProgressive supranuclear palsyParkinson's diseaseAmyotrophic lateral sclerosisMultiple sclerosisNeurodegenerative diseaseLongevityPLCG2Phospholipase C Gamma 2The 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 PLC gamma 2 pathway as drug-target.SPRINGER2019info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttps://iibsantpau.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=2515http://ddd.uab.cat/record/226469ACTA NEUROPATHOLOGICAISSN: 00016322ISSNe: 14320533reponame:r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pauinstname:Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau)Inglésinfo:eu-repo/semantics/openAccessoai:iibsantpau.fundanetsuite.com:p25152026-06-14T12:41:47Z
dc.title.none.fl_str_mv	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
title	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
spellingShingle	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, SJ 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
title_short	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
title_full	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
title_fullStr	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
title_full_unstemmed	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
title_sort	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
dc.creator.none.fl_str_mv	van der Lee, SJ Conway, OJ Jansen, I Carrasquillo, MM Kleineidam, L van den Akker, E Hernandez, I van Eijk, KR Stringa, N Chen, JA Zettergren, A Andlauer, TFM Diez-Fairen, M Simon-Sanchez, J Lleo, A Zetterberg, H Nygaard, M Blauwendraat, C Savage, JE Mengel-From, J Moreno-Grau, S Wagner, M Fortea, J Keogh, MJ Blennow, K Skoog, I Friese, MA Pletnikova, O Zulaica, M Lage, C de Rojas, I Riedel-Heller, S Illan-Gala, I Wei, W Jeune, B Orellana, A Bergh, FT Wang, X Hulsman, M Beker, N Tesi, N Morris, CM Indakoetxea, B Collij, LE Scherer, M Morenas-Rodriguez, E Ironside, JW van Berckel, BNM Alcolea, D Wiendl, H Strickland, SL Pastor, P Rodriguez Rodriguez, E Boeve, BF Petersen, RC Ferman, TJ van Gerpen, JA Reinders, MJT Uitti, RJ Tarraga, L Maier, W Dols-Icardo, O Kawalia, A Dalmasso, MC Boada, M Zettl, UK van Schoor, NM Beekman, M Allen, M Masliah, E de Munain, AL Pantelyat, A Wszolek, ZK Ross, OA Dickson, DW Graff-Radford, NR Knopman, D Rademakers, R Lemstra, AW Pijnenburg, YAL Scheltens, P Gasser, T Chinnery, PF Hemmer, B Huisman, MA Troncoso, J Moreno, F Nohr, EA Sorensen, TIA Heutink, P Sanchez-Juan, P Posthuma, D Clarimon, J Christensen, K Ertekin-Taner, N Scholz, SW Ramirez, A Ruiz, A Slagboom, E van der Flier, WM Holstege, H
author	van der Lee, SJ
author_facet	van der Lee, SJ Conway, OJ Jansen, I Carrasquillo, MM Kleineidam, L van den Akker, E Hernandez, I van Eijk, KR Stringa, N Chen, JA Zettergren, A Andlauer, TFM Diez-Fairen, M Simon-Sanchez, J Lleo, A Zetterberg, H Nygaard, M Blauwendraat, C Savage, JE Mengel-From, J Moreno-Grau, S Wagner, M Fortea, J Keogh, MJ Blennow, K Skoog, I Friese, MA Pletnikova, O Zulaica, M Lage, C de Rojas, I Riedel-Heller, S Illan-Gala, I Wei, W Jeune, B Orellana, A Bergh, FT Wang, X Hulsman, M Beker, N Tesi, N Morris, CM Indakoetxea, B Collij, LE Scherer, M Morenas-Rodriguez, E Ironside, JW van Berckel, BNM Alcolea, D Wiendl, H Strickland, SL Pastor, P Rodriguez Rodriguez, E Boeve, BF Petersen, RC Ferman, TJ van Gerpen, JA Reinders, MJT Uitti, RJ Tarraga, L Maier, W Dols-Icardo, O Kawalia, A Dalmasso, MC Boada, M Zettl, UK van Schoor, NM Beekman, M Allen, M Masliah, E de Munain, AL Pantelyat, A Wszolek, ZK Ross, OA Dickson, DW Graff-Radford, NR Knopman, D Rademakers, R Lemstra, AW Pijnenburg, YAL Scheltens, P Gasser, T Chinnery, PF Hemmer, B Huisman, MA Troncoso, J Moreno, F Nohr, EA Sorensen, TIA Heutink, P Sanchez-Juan, P Posthuma, D Clarimon, J Christensen, K Ertekin-Taner, N Scholz, SW Ramirez, A Ruiz, A Slagboom, E van der Flier, WM Holstege, H
author_role	author
author2	Conway, OJ Jansen, I Carrasquillo, MM Kleineidam, L van den Akker, E Hernandez, I van Eijk, KR Stringa, N Chen, JA Zettergren, A Andlauer, TFM Diez-Fairen, M Simon-Sanchez, J Lleo, A Zetterberg, H Nygaard, M Blauwendraat, C Savage, JE Mengel-From, J Moreno-Grau, S Wagner, M Fortea, J Keogh, MJ Blennow, K Skoog, I Friese, MA Pletnikova, O Zulaica, M Lage, C de Rojas, I Riedel-Heller, S Illan-Gala, I Wei, W Jeune, B Orellana, A Bergh, FT Wang, X Hulsman, M Beker, N Tesi, N Morris, CM Indakoetxea, B Collij, LE Scherer, M Morenas-Rodriguez, E Ironside, JW van Berckel, BNM Alcolea, D Wiendl, H Strickland, SL Pastor, P Rodriguez Rodriguez, E Boeve, BF Petersen, RC Ferman, TJ van Gerpen, JA Reinders, MJT Uitti, RJ Tarraga, L Maier, W Dols-Icardo, O Kawalia, A Dalmasso, MC Boada, M Zettl, UK van Schoor, NM Beekman, M Allen, M Masliah, E de Munain, AL Pantelyat, A Wszolek, ZK Ross, OA Dickson, DW Graff-Radford, NR Knopman, D Rademakers, R Lemstra, AW Pijnenburg, YAL Scheltens, P Gasser, T Chinnery, PF Hemmer, B Huisman, MA Troncoso, J Moreno, F Nohr, EA Sorensen, TIA Heutink, P Sanchez-Juan, P Posthuma, D Clarimon, J Christensen, K Ertekin-Taner, N Scholz, SW Ramirez, A Ruiz, A Slagboom, E van der Flier, WM Holstege, H
author2_role	author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author
dc.subject.none.fl_str_mv	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
topic	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
description	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 PLC gamma 2 pathway as drug-target.
publishDate	2019
dc.date.none.fl_str_mv	2019
dc.type.none.fl_str_mv	info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion
format	article
status_str	publishedVersion
dc.identifier.none.fl_str_mv	https://iibsantpau.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=2515 http://ddd.uab.cat/record/226469
url	https://iibsantpau.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=2515 http://ddd.uab.cat/record/226469
dc.language.none.fl_str_mv	Inglés
language_invalid_str_mv	Inglés
dc.rights.none.fl_str_mv	info:eu-repo/semantics/openAccess
eu_rights_str_mv	openAccess
dc.publisher.none.fl_str_mv	SPRINGER
publisher.none.fl_str_mv	SPRINGER
dc.source.none.fl_str_mv	ACTA NEUROPATHOLOGICA ISSN: 00016322 ISSNe: 14320533 reponame:r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau instname:Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau)
instname_str	Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau)
reponame_str	r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau
collection	r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score	15.811543

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

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