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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 stud...
| Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Formato: | Online Artículo Texto |
| Lenguaje: | English |
| Publicado: |
Springer Berlin Heidelberg
2019
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| Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6660501/ https://www.ncbi.nlm.nih.gov/pubmed/31131421 http://dx.doi.org/10.1007/s00401-019-02026-8 |
| _version_ | 1783439311843098624 |
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| author | 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 Lage, Carmen de Rojas, Itziar Riedel-Heller, Steffi Illán-Gala, Ignacio Wei, Wei Jeune, Bernard Orellana, Adelina Then Bergh, Florian Wang, Xue Hulsman, Marc Beker, Nina Tesi, Niccolo Morris, Christopher M. Indakoetxea, Begoña Collij, Lyduine E. Scherer, Martin Morenas-Rodríguez, Estrella Ironside, James W. van Berckel, Bart N. M. Alcolea, Daniel Wiendl, Heinz Strickland, Samantha L. Pastor, Pau Rodríguez Rodríguez, Eloy Boeve, Bradley F. Petersen, Ronald C. Ferman, Tanis J. van Gerpen, Jay A. Reinders, Marcel J. T. Uitti, Ryan J. Tárraga, Lluís Maier, Wolfgang Dols-Icardo, Oriol Kawalia, Amit Dalmasso, Maria Carolina Boada, Mercè Zettl, Uwe K. van Schoor, Natasja M. Beekman, Marian Allen, Mariet Masliah, Eliezer de Munain, Adolfo López Pantelyat, Alexander Wszolek, Zbigniew K. Ross, Owen A. Dickson, Dennis W. Graff-Radford, Neill R. Knopman, David Rademakers, Rosa Lemstra, Afina W. Pijnenburg, Yolande A. L. Scheltens, Philip Gasser, Thomas Chinnery, Patrick F Hemmer, Bernhard Huisman, Martijn A. Troncoso, Juan Moreno, Fermin Nohr, Ellen A. Sørensen, Thorkild I. A. Heutink, Peter Sánchez-Juan, Pascual Posthuma, Danielle Clarimón, Jordi Christensen, Kaare Ertekin-Taner, Nilüfer Scholz, Sonja W. Ramirez, Alfredo Ruiz, Agustín Slagboom, Eline van der Flier, Wiesje M. Holstege, Henne |
| author_facet | 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 Lage, Carmen de Rojas, Itziar Riedel-Heller, Steffi Illán-Gala, Ignacio Wei, Wei Jeune, Bernard Orellana, Adelina Then Bergh, Florian Wang, Xue Hulsman, Marc Beker, Nina Tesi, Niccolo Morris, Christopher M. Indakoetxea, Begoña Collij, Lyduine E. Scherer, Martin Morenas-Rodríguez, Estrella Ironside, James W. van Berckel, Bart N. M. Alcolea, Daniel Wiendl, Heinz Strickland, Samantha L. Pastor, Pau Rodríguez Rodríguez, Eloy Boeve, Bradley F. Petersen, Ronald C. Ferman, Tanis J. van Gerpen, Jay A. Reinders, Marcel J. T. Uitti, Ryan J. Tárraga, Lluís Maier, Wolfgang Dols-Icardo, Oriol Kawalia, Amit Dalmasso, Maria Carolina Boada, Mercè Zettl, Uwe K. van Schoor, Natasja M. Beekman, Marian Allen, Mariet Masliah, Eliezer de Munain, Adolfo López Pantelyat, Alexander Wszolek, Zbigniew K. Ross, Owen A. Dickson, Dennis W. Graff-Radford, Neill R. Knopman, David Rademakers, Rosa Lemstra, Afina W. Pijnenburg, Yolande A. L. Scheltens, Philip Gasser, Thomas Chinnery, Patrick F Hemmer, Bernhard Huisman, Martijn A. Troncoso, Juan Moreno, Fermin Nohr, Ellen A. Sørensen, Thorkild I. A. Heutink, Peter Sánchez-Juan, Pascual Posthuma, Danielle Clarimón, Jordi Christensen, Kaare Ertekin-Taner, Nilüfer Scholz, Sonja W. Ramirez, Alfredo Ruiz, Agustín Slagboom, Eline van der Flier, Wiesje M. Holstege, Henne |
| author_sort | van der Lee, Sven J. |
| collection | PubMed |
| 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 PLCγ2 pathway as drug-target. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00401-019-02026-8) contains supplementary material, which is available to authorized users. |
| format | Online Article Text |
| id | pubmed-6660501 |
| institution | National Center for Biotechnology Information |
| language | English |
| publishDate | 2019 |
| publisher | Springer Berlin Heidelberg |
| record_format | MEDLINE/PubMed |
| spelling | pubmed-66605012019-08-07 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. 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 Lage, Carmen de Rojas, Itziar Riedel-Heller, Steffi Illán-Gala, Ignacio Wei, Wei Jeune, Bernard Orellana, Adelina Then Bergh, Florian Wang, Xue Hulsman, Marc Beker, Nina Tesi, Niccolo Morris, Christopher M. Indakoetxea, Begoña Collij, Lyduine E. Scherer, Martin Morenas-Rodríguez, Estrella Ironside, James W. van Berckel, Bart N. M. Alcolea, Daniel Wiendl, Heinz Strickland, Samantha L. Pastor, Pau Rodríguez Rodríguez, Eloy Boeve, Bradley F. Petersen, Ronald C. Ferman, Tanis J. van Gerpen, Jay A. Reinders, Marcel J. T. Uitti, Ryan J. Tárraga, Lluís Maier, Wolfgang Dols-Icardo, Oriol Kawalia, Amit Dalmasso, Maria Carolina Boada, Mercè Zettl, Uwe K. van Schoor, Natasja M. Beekman, Marian Allen, Mariet Masliah, Eliezer de Munain, Adolfo López Pantelyat, Alexander Wszolek, Zbigniew K. Ross, Owen A. Dickson, Dennis W. Graff-Radford, Neill R. Knopman, David Rademakers, Rosa Lemstra, Afina W. Pijnenburg, Yolande A. L. Scheltens, Philip Gasser, Thomas Chinnery, Patrick F Hemmer, Bernhard Huisman, Martijn A. Troncoso, Juan Moreno, Fermin Nohr, Ellen A. Sørensen, Thorkild I. A. Heutink, Peter Sánchez-Juan, Pascual Posthuma, Danielle Clarimón, Jordi Christensen, Kaare Ertekin-Taner, Nilüfer Scholz, Sonja W. Ramirez, Alfredo Ruiz, Agustín Slagboom, Eline van der Flier, Wiesje M. Holstege, Henne Acta Neuropathol Original Paper 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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00401-019-02026-8) contains supplementary material, which is available to authorized users. Springer Berlin Heidelberg 2019-05-26 2019 /pmc/articles/PMC6660501/ /pubmed/31131421 http://dx.doi.org/10.1007/s00401-019-02026-8 Text en © The Author(s) 2019 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. |
| spellingShingle | Original Paper 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 Lage, Carmen de Rojas, Itziar Riedel-Heller, Steffi Illán-Gala, Ignacio Wei, Wei Jeune, Bernard Orellana, Adelina Then Bergh, Florian Wang, Xue Hulsman, Marc Beker, Nina Tesi, Niccolo Morris, Christopher M. Indakoetxea, Begoña Collij, Lyduine E. Scherer, Martin Morenas-Rodríguez, Estrella Ironside, James W. van Berckel, Bart N. M. Alcolea, Daniel Wiendl, Heinz Strickland, Samantha L. Pastor, Pau Rodríguez Rodríguez, Eloy Boeve, Bradley F. Petersen, Ronald C. Ferman, Tanis J. van Gerpen, Jay A. Reinders, Marcel J. T. Uitti, Ryan J. Tárraga, Lluís Maier, Wolfgang Dols-Icardo, Oriol Kawalia, Amit Dalmasso, Maria Carolina Boada, Mercè Zettl, Uwe K. van Schoor, Natasja M. Beekman, Marian Allen, Mariet Masliah, Eliezer de Munain, Adolfo López Pantelyat, Alexander Wszolek, Zbigniew K. Ross, Owen A. Dickson, Dennis W. Graff-Radford, Neill R. Knopman, David Rademakers, Rosa Lemstra, Afina W. Pijnenburg, Yolande A. L. Scheltens, Philip Gasser, Thomas Chinnery, Patrick F Hemmer, Bernhard Huisman, Martijn A. Troncoso, Juan Moreno, Fermin Nohr, Ellen A. Sørensen, Thorkild I. A. Heutink, Peter Sánchez-Juan, Pascual Posthuma, Danielle Clarimón, Jordi Christensen, Kaare Ertekin-Taner, Nilüfer Scholz, Sonja W. Ramirez, Alfredo Ruiz, Agustín Slagboom, Eline van der Flier, Wiesje M. Holstege, Henne 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 |
| 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_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_sort | nonsynonymous mutation in plcg2 reduces the risk of alzheimer’s disease, dementia with lewy bodies and frontotemporal dementia, and increases the likelihood of longevity |
| topic | Original Paper |
| url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6660501/ https://www.ncbi.nlm.nih.gov/pubmed/31131421 http://dx.doi.org/10.1007/s00401-019-02026-8 |
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anonsynonymousmutationinplcg2reducestheriskofalzheimersdiseasedementiawithlewybodiesandfrontotemporaldementiaandincreasesthelikelihoodoflongevity AT vanschoornatasjam anonsynonymousmutationinplcg2reducestheriskofalzheimersdiseasedementiawithlewybodiesandfrontotemporaldementiaandincreasesthelikelihoodoflongevity AT beekmanmarian anonsynonymousmutationinplcg2reducestheriskofalzheimersdiseasedementiawithlewybodiesandfrontotemporaldementiaandincreasesthelikelihoodoflongevity AT allenmariet anonsynonymousmutationinplcg2reducestheriskofalzheimersdiseasedementiawithlewybodiesandfrontotemporaldementiaandincreasesthelikelihoodoflongevity AT masliaheliezer anonsynonymousmutationinplcg2reducestheriskofalzheimersdiseasedementiawithlewybodiesandfrontotemporaldementiaandincreasesthelikelihoodoflongevity AT demunainadolfolopez anonsynonymousmutationinplcg2reducestheriskofalzheimersdiseasedementiawithlewybodiesandfrontotemporaldementiaandincreasesthelikelihoodoflongevity AT pantelyatalexander anonsynonymousmutationinplcg2reducestheriskofalzheimersdiseasedementiawithlewybodiesandfrontotemporaldementiaandincreasesthelikelihoodoflongevity AT wszolekzbigniewk anonsynonymousmutationinplcg2reducestheriskofalzheimersdiseasedementiawithlewybodiesandfrontotemporaldementiaandincreasesthelikelihoodoflongevity AT rossowena anonsynonymousmutationinplcg2reducestheriskofalzheimersdiseasedementiawithlewybodiesandfrontotemporaldementiaandincreasesthelikelihoodoflongevity AT dicksondennisw anonsynonymousmutationinplcg2reducestheriskofalzheimersdiseasedementiawithlewybodiesandfrontotemporaldementiaandincreasesthelikelihoodoflongevity AT graffradfordneillr anonsynonymousmutationinplcg2reducestheriskofalzheimersdiseasedementiawithlewybodiesandfrontotemporaldementiaandincreasesthelikelihoodoflongevity AT knopmandavid anonsynonymousmutationinplcg2reducestheriskofalzheimersdiseasedementiawithlewybodiesandfrontotemporaldementiaandincreasesthelikelihoodoflongevity AT rademakersrosa anonsynonymousmutationinplcg2reducestheriskofalzheimersdiseasedementiawithlewybodiesandfrontotemporaldementiaandincreasesthelikelihoodoflongevity AT lemstraafinaw anonsynonymousmutationinplcg2reducestheriskofalzheimersdiseasedementiawithlewybodiesandfrontotemporaldementiaandincreasesthelikelihoodoflongevity AT pijnenburgyolandeal anonsynonymousmutationinplcg2reducestheriskofalzheimersdiseasedementiawithlewybodiesandfrontotemporaldementiaandincreasesthelikelihoodoflongevity AT scheltensphilip anonsynonymousmutationinplcg2reducestheriskofalzheimersdiseasedementiawithlewybodiesandfrontotemporaldementiaandincreasesthelikelihoodoflongevity AT gasserthomas anonsynonymousmutationinplcg2reducestheriskofalzheimersdiseasedementiawithlewybodiesandfrontotemporaldementiaandincreasesthelikelihoodoflongevity AT chinnerypatrickf anonsynonymousmutationinplcg2reducestheriskofalzheimersdiseasedementiawithlewybodiesandfrontotemporaldementiaandincreasesthelikelihoodoflongevity AT hemmerbernhard anonsynonymousmutationinplcg2reducestheriskofalzheimersdiseasedementiawithlewybodiesandfrontotemporaldementiaandincreasesthelikelihoodoflongevity AT huismanmartijna anonsynonymousmutationinplcg2reducestheriskofalzheimersdiseasedementiawithlewybodiesandfrontotemporaldementiaandincreasesthelikelihoodoflongevity AT troncosojuan anonsynonymousmutationinplcg2reducestheriskofalzheimersdiseasedementiawithlewybodiesandfrontotemporaldementiaandincreasesthelikelihoodoflongevity AT morenofermin anonsynonymousmutationinplcg2reducestheriskofalzheimersdiseasedementiawithlewybodiesandfrontotemporaldementiaandincreasesthelikelihoodoflongevity AT nohrellena anonsynonymousmutationinplcg2reducestheriskofalzheimersdiseasedementiawithlewybodiesandfrontotemporaldementiaandincreasesthelikelihoodoflongevity AT sørensenthorkildia anonsynonymousmutationinplcg2reducestheriskofalzheimersdiseasedementiawithlewybodiesandfrontotemporaldementiaandincreasesthelikelihoodoflongevity AT heutinkpeter anonsynonymousmutationinplcg2reducestheriskofalzheimersdiseasedementiawithlewybodiesandfrontotemporaldementiaandincreasesthelikelihoodoflongevity AT sanchezjuanpascual anonsynonymousmutationinplcg2reducestheriskofalzheimersdiseasedementiawithlewybodiesandfrontotemporaldementiaandincreasesthelikelihoodoflongevity AT posthumadanielle anonsynonymousmutationinplcg2reducestheriskofalzheimersdiseasedementiawithlewybodiesandfrontotemporaldementiaandincreasesthelikelihoodoflongevity AT anonsynonymousmutationinplcg2reducestheriskofalzheimersdiseasedementiawithlewybodiesandfrontotemporaldementiaandincreasesthelikelihoodoflongevity AT clarimonjordi anonsynonymousmutationinplcg2reducestheriskofalzheimersdiseasedementiawithlewybodiesandfrontotemporaldementiaandincreasesthelikelihoodoflongevity AT christensenkaare anonsynonymousmutationinplcg2reducestheriskofalzheimersdiseasedementiawithlewybodiesandfrontotemporaldementiaandincreasesthelikelihoodoflongevity AT ertekintanernilufer anonsynonymousmutationinplcg2reducestheriskofalzheimersdiseasedementiawithlewybodiesandfrontotemporaldementiaandincreasesthelikelihoodoflongevity AT scholzsonjaw anonsynonymousmutationinplcg2reducestheriskofalzheimersdiseasedementiawithlewybodiesandfrontotemporaldementiaandincreasesthelikelihoodoflongevity AT ramirezalfredo anonsynonymousmutationinplcg2reducestheriskofalzheimersdiseasedementiawithlewybodiesandfrontotemporaldementiaandincreasesthelikelihoodoflongevity AT ruizagustin anonsynonymousmutationinplcg2reducestheriskofalzheimersdiseasedementiawithlewybodiesandfrontotemporaldementiaandincreasesthelikelihoodoflongevity AT slagboomeline anonsynonymousmutationinplcg2reducestheriskofalzheimersdiseasedementiawithlewybodiesandfrontotemporaldementiaandincreasesthelikelihoodoflongevity AT vanderflierwiesjem anonsynonymousmutationinplcg2reducestheriskofalzheimersdiseasedementiawithlewybodiesandfrontotemporaldementiaandincreasesthelikelihoodoflongevity AT holstegehenne anonsynonymousmutationinplcg2reducestheriskofalzheimersdiseasedementiawithlewybodiesandfrontotemporaldementiaandincreasesthelikelihoodoflongevity AT vanderleesvenj nonsynonymousmutationinplcg2reducestheriskofalzheimersdiseasedementiawithlewybodiesandfrontotemporaldementiaandincreasesthelikelihoodoflongevity AT conwayoliviaj nonsynonymousmutationinplcg2reducestheriskofalzheimersdiseasedementiawithlewybodiesandfrontotemporaldementiaandincreasesthelikelihoodoflongevity AT janseniris nonsynonymousmutationinplcg2reducestheriskofalzheimersdiseasedementiawithlewybodiesandfrontotemporaldementiaandincreasesthelikelihoodoflongevity AT carrasquillominervam nonsynonymousmutationinplcg2reducestheriskofalzheimersdiseasedementiawithlewybodiesandfrontotemporaldementiaandincreasesthelikelihoodoflongevity AT kleineidamluca nonsynonymousmutationinplcg2reducestheriskofalzheimersdiseasedementiawithlewybodiesandfrontotemporaldementiaandincreasesthelikelihoodoflongevity AT vandenakkererik nonsynonymousmutationinplcg2reducestheriskofalzheimersdiseasedementiawithlewybodiesandfrontotemporaldementiaandincreasesthelikelihoodoflongevity AT hernandezisabel nonsynonymousmutationinplcg2reducestheriskofalzheimersdiseasedementiawithlewybodiesandfrontotemporaldementiaandincreasesthelikelihoodoflongevity AT vaneijkkristelr nonsynonymousmutationinplcg2reducestheriskofalzheimersdiseasedementiawithlewybodiesandfrontotemporaldementiaandincreasesthelikelihoodoflongevity AT stringanajada nonsynonymousmutationinplcg2reducestheriskofalzheimersdiseasedementiawithlewybodiesandfrontotemporaldementiaandincreasesthelikelihoodoflongevity AT chenjasona nonsynonymousmutationinplcg2reducestheriskofalzheimersdiseasedementiawithlewybodiesandfrontotemporaldementiaandincreasesthelikelihoodoflongevity AT zettergrenanna nonsynonymousmutationinplcg2reducestheriskofalzheimersdiseasedementiawithlewybodiesandfrontotemporaldementiaandincreasesthelikelihoodoflongevity AT andlauertillfm nonsynonymousmutationinplcg2reducestheriskofalzheimersdiseasedementiawithlewybodiesandfrontotemporaldementiaandincreasesthelikelihoodoflongevity AT diezfairenmonica nonsynonymousmutationinplcg2reducestheriskofalzheimersdiseasedementiawithlewybodiesandfrontotemporaldementiaandincreasesthelikelihoodoflongevity AT simonsanchezjavier nonsynonymousmutationinplcg2reducestheriskofalzheimersdiseasedementiawithlewybodiesandfrontotemporaldementiaandincreasesthelikelihoodoflongevity AT lleoalberto nonsynonymousmutationinplcg2reducestheriskofalzheimersdiseasedementiawithlewybodiesandfrontotemporaldementiaandincreasesthelikelihoodoflongevity AT zetterberghenrik nonsynonymousmutationinplcg2reducestheriskofalzheimersdiseasedementiawithlewybodiesandfrontotemporaldementiaandincreasesthelikelihoodoflongevity AT nygaardmarianne nonsynonymousmutationinplcg2reducestheriskofalzheimersdiseasedementiawithlewybodiesandfrontotemporaldementiaandincreasesthelikelihoodoflongevity AT blauwendraatcornelis nonsynonymousmutationinplcg2reducestheriskofalzheimersdiseasedementiawithlewybodiesandfrontotemporaldementiaandincreasesthelikelihoodoflongevity AT savagejeannee nonsynonymousmutationinplcg2reducestheriskofalzheimersdiseasedementiawithlewybodiesandfrontotemporaldementiaandincreasesthelikelihoodoflongevity AT mengelfromjonas nonsynonymousmutationinplcg2reducestheriskofalzheimersdiseasedementiawithlewybodiesandfrontotemporaldementiaandincreasesthelikelihoodoflongevity AT morenograusonia nonsynonymousmutationinplcg2reducestheriskofalzheimersdiseasedementiawithlewybodiesandfrontotemporaldementiaandincreasesthelikelihoodoflongevity AT wagnermichael nonsynonymousmutationinplcg2reducestheriskofalzheimersdiseasedementiawithlewybodiesandfrontotemporaldementiaandincreasesthelikelihoodoflongevity AT forteajuan nonsynonymousmutationinplcg2reducestheriskofalzheimersdiseasedementiawithlewybodiesandfrontotemporaldementiaandincreasesthelikelihoodoflongevity AT keoghmichaelj nonsynonymousmutationinplcg2reducestheriskofalzheimersdiseasedementiawithlewybodiesandfrontotemporaldementiaandincreasesthelikelihoodoflongevity AT blennowkaj nonsynonymousmutationinplcg2reducestheriskofalzheimersdiseasedementiawithlewybodiesandfrontotemporaldementiaandincreasesthelikelihoodoflongevity AT skoogingmar nonsynonymousmutationinplcg2reducestheriskofalzheimersdiseasedementiawithlewybodiesandfrontotemporaldementiaandincreasesthelikelihoodoflongevity AT friesemanuela nonsynonymousmutationinplcg2reducestheriskofalzheimersdiseasedementiawithlewybodiesandfrontotemporaldementiaandincreasesthelikelihoodoflongevity AT pletnikovaolga nonsynonymousmutationinplcg2reducestheriskofalzheimersdiseasedementiawithlewybodiesandfrontotemporaldementiaandincreasesthelikelihoodoflongevity AT zulaicamiren nonsynonymousmutationinplcg2reducestheriskofalzheimersdiseasedementiawithlewybodiesandfrontotemporaldementiaandincreasesthelikelihoodoflongevity AT lagecarmen nonsynonymousmutationinplcg2reducestheriskofalzheimersdiseasedementiawithlewybodiesandfrontotemporaldementiaandincreasesthelikelihoodoflongevity AT derojasitziar nonsynonymousmutationinplcg2reducestheriskofalzheimersdiseasedementiawithlewybodiesandfrontotemporaldementiaandincreasesthelikelihoodoflongevity AT riedelhellersteffi nonsynonymousmutationinplcg2reducestheriskofalzheimersdiseasedementiawithlewybodiesandfrontotemporaldementiaandincreasesthelikelihoodoflongevity AT illangalaignacio nonsynonymousmutationinplcg2reducestheriskofalzheimersdiseasedementiawithlewybodiesandfrontotemporaldementiaandincreasesthelikelihoodoflongevity AT weiwei nonsynonymousmutationinplcg2reducestheriskofalzheimersdiseasedementiawithlewybodiesandfrontotemporaldementiaandincreasesthelikelihoodoflongevity AT jeunebernard nonsynonymousmutationinplcg2reducestheriskofalzheimersdiseasedementiawithlewybodiesandfrontotemporaldementiaandincreasesthelikelihoodoflongevity AT orellanaadelina nonsynonymousmutationinplcg2reducestheriskofalzheimersdiseasedementiawithlewybodiesandfrontotemporaldementiaandincreasesthelikelihoodoflongevity AT thenberghflorian nonsynonymousmutationinplcg2reducestheriskofalzheimersdiseasedementiawithlewybodiesandfrontotemporaldementiaandincreasesthelikelihoodoflongevity AT wangxue nonsynonymousmutationinplcg2reducestheriskofalzheimersdiseasedementiawithlewybodiesandfrontotemporaldementiaandincreasesthelikelihoodoflongevity AT hulsmanmarc nonsynonymousmutationinplcg2reducestheriskofalzheimersdiseasedementiawithlewybodiesandfrontotemporaldementiaandincreasesthelikelihoodoflongevity AT bekernina nonsynonymousmutationinplcg2reducestheriskofalzheimersdiseasedementiawithlewybodiesandfrontotemporaldementiaandincreasesthelikelihoodoflongevity AT tesiniccolo nonsynonymousmutationinplcg2reducestheriskofalzheimersdiseasedementiawithlewybodiesandfrontotemporaldementiaandincreasesthelikelihoodoflongevity AT morrischristopherm nonsynonymousmutationinplcg2reducestheriskofalzheimersdiseasedementiawithlewybodiesandfrontotemporaldementiaandincreasesthelikelihoodoflongevity AT indakoetxeabegona nonsynonymousmutationinplcg2reducestheriskofalzheimersdiseasedementiawithlewybodiesandfrontotemporaldementiaandincreasesthelikelihoodoflongevity AT collijlyduinee nonsynonymousmutationinplcg2reducestheriskofalzheimersdiseasedementiawithlewybodiesandfrontotemporaldementiaandincreasesthelikelihoodoflongevity AT scherermartin nonsynonymousmutationinplcg2reducestheriskofalzheimersdiseasedementiawithlewybodiesandfrontotemporaldementiaandincreasesthelikelihoodoflongevity AT morenasrodriguezestrella nonsynonymousmutationinplcg2reducestheriskofalzheimersdiseasedementiawithlewybodiesandfrontotemporaldementiaandincreasesthelikelihoodoflongevity AT ironsidejamesw nonsynonymousmutationinplcg2reducestheriskofalzheimersdiseasedementiawithlewybodiesandfrontotemporaldementiaandincreasesthelikelihoodoflongevity AT vanberckelbartnm nonsynonymousmutationinplcg2reducestheriskofalzheimersdiseasedementiawithlewybodiesandfrontotemporaldementiaandincreasesthelikelihoodoflongevity AT alcoleadaniel nonsynonymousmutationinplcg2reducestheriskofalzheimersdiseasedementiawithlewybodiesandfrontotemporaldementiaandincreasesthelikelihoodoflongevity AT wiendlheinz nonsynonymousmutationinplcg2reducestheriskofalzheimersdiseasedementiawithlewybodiesandfrontotemporaldementiaandincreasesthelikelihoodoflongevity AT stricklandsamanthal nonsynonymousmutationinplcg2reducestheriskofalzheimersdiseasedementiawithlewybodiesandfrontotemporaldementiaandincreasesthelikelihoodoflongevity AT pastorpau nonsynonymousmutationinplcg2reducestheriskofalzheimersdiseasedementiawithlewybodiesandfrontotemporaldementiaandincreasesthelikelihoodoflongevity AT rodriguezrodriguezeloy nonsynonymousmutationinplcg2reducestheriskofalzheimersdiseasedementiawithlewybodiesandfrontotemporaldementiaandincreasesthelikelihoodoflongevity AT nonsynonymousmutationinplcg2reducestheriskofalzheimersdiseasedementiawithlewybodiesandfrontotemporaldementiaandincreasesthelikelihoodoflongevity AT nonsynonymousmutationinplcg2reducestheriskofalzheimersdiseasedementiawithlewybodiesandfrontotemporaldementiaandincreasesthelikelihoodoflongevity AT nonsynonymousmutationinplcg2reducestheriskofalzheimersdiseasedementiawithlewybodiesandfrontotemporaldementiaandincreasesthelikelihoodoflongevity AT nonsynonymousmutationinplcg2reducestheriskofalzheimersdiseasedementiawithlewybodiesandfrontotemporaldementiaandincreasesthelikelihoodoflongevity AT nonsynonymousmutationinplcg2reducestheriskofalzheimersdiseasedementiawithlewybodiesandfrontotemporaldementiaandincreasesthelikelihoodoflongevity AT nonsynonymousmutationinplcg2reducestheriskofalzheimersdiseasedementiawithlewybodiesandfrontotemporaldementiaandincreasesthelikelihoodoflongevity AT boevebradleyf nonsynonymousmutationinplcg2reducestheriskofalzheimersdiseasedementiawithlewybodiesandfrontotemporaldementiaandincreasesthelikelihoodoflongevity AT petersenronaldc nonsynonymousmutationinplcg2reducestheriskofalzheimersdiseasedementiawithlewybodiesandfrontotemporaldementiaandincreasesthelikelihoodoflongevity AT fermantanisj nonsynonymousmutationinplcg2reducestheriskofalzheimersdiseasedementiawithlewybodiesandfrontotemporaldementiaandincreasesthelikelihoodoflongevity AT vangerpenjaya nonsynonymousmutationinplcg2reducestheriskofalzheimersdiseasedementiawithlewybodiesandfrontotemporaldementiaandincreasesthelikelihoodoflongevity AT reindersmarceljt nonsynonymousmutationinplcg2reducestheriskofalzheimersdiseasedementiawithlewybodiesandfrontotemporaldementiaandincreasesthelikelihoodoflongevity AT uittiryanj nonsynonymousmutationinplcg2reducestheriskofalzheimersdiseasedementiawithlewybodiesandfrontotemporaldementiaandincreasesthelikelihoodoflongevity AT tarragalluis nonsynonymousmutationinplcg2reducestheriskofalzheimersdiseasedementiawithlewybodiesandfrontotemporaldementiaandincreasesthelikelihoodoflongevity AT maierwolfgang nonsynonymousmutationinplcg2reducestheriskofalzheimersdiseasedementiawithlewybodiesandfrontotemporaldementiaandincreasesthelikelihoodoflongevity AT dolsicardooriol nonsynonymousmutationinplcg2reducestheriskofalzheimersdiseasedementiawithlewybodiesandfrontotemporaldementiaandincreasesthelikelihoodoflongevity AT kawaliaamit nonsynonymousmutationinplcg2reducestheriskofalzheimersdiseasedementiawithlewybodiesandfrontotemporaldementiaandincreasesthelikelihoodoflongevity AT dalmassomariacarolina nonsynonymousmutationinplcg2reducestheriskofalzheimersdiseasedementiawithlewybodiesandfrontotemporaldementiaandincreasesthelikelihoodoflongevity AT boadamerce nonsynonymousmutationinplcg2reducestheriskofalzheimersdiseasedementiawithlewybodiesandfrontotemporaldementiaandincreasesthelikelihoodoflongevity AT zettluwek nonsynonymousmutationinplcg2reducestheriskofalzheimersdiseasedementiawithlewybodiesandfrontotemporaldementiaandincreasesthelikelihoodoflongevity AT vanschoornatasjam nonsynonymousmutationinplcg2reducestheriskofalzheimersdiseasedementiawithlewybodiesandfrontotemporaldementiaandincreasesthelikelihoodoflongevity AT beekmanmarian nonsynonymousmutationinplcg2reducestheriskofalzheimersdiseasedementiawithlewybodiesandfrontotemporaldementiaandincreasesthelikelihoodoflongevity AT allenmariet nonsynonymousmutationinplcg2reducestheriskofalzheimersdiseasedementiawithlewybodiesandfrontotemporaldementiaandincreasesthelikelihoodoflongevity AT masliaheliezer nonsynonymousmutationinplcg2reducestheriskofalzheimersdiseasedementiawithlewybodiesandfrontotemporaldementiaandincreasesthelikelihoodoflongevity AT demunainadolfolopez nonsynonymousmutationinplcg2reducestheriskofalzheimersdiseasedementiawithlewybodiesandfrontotemporaldementiaandincreasesthelikelihoodoflongevity AT pantelyatalexander nonsynonymousmutationinplcg2reducestheriskofalzheimersdiseasedementiawithlewybodiesandfrontotemporaldementiaandincreasesthelikelihoodoflongevity AT wszolekzbigniewk nonsynonymousmutationinplcg2reducestheriskofalzheimersdiseasedementiawithlewybodiesandfrontotemporaldementiaandincreasesthelikelihoodoflongevity AT rossowena nonsynonymousmutationinplcg2reducestheriskofalzheimersdiseasedementiawithlewybodiesandfrontotemporaldementiaandincreasesthelikelihoodoflongevity AT dicksondennisw nonsynonymousmutationinplcg2reducestheriskofalzheimersdiseasedementiawithlewybodiesandfrontotemporaldementiaandincreasesthelikelihoodoflongevity AT graffradfordneillr nonsynonymousmutationinplcg2reducestheriskofalzheimersdiseasedementiawithlewybodiesandfrontotemporaldementiaandincreasesthelikelihoodoflongevity AT knopmandavid nonsynonymousmutationinplcg2reducestheriskofalzheimersdiseasedementiawithlewybodiesandfrontotemporaldementiaandincreasesthelikelihoodoflongevity AT rademakersrosa nonsynonymousmutationinplcg2reducestheriskofalzheimersdiseasedementiawithlewybodiesandfrontotemporaldementiaandincreasesthelikelihoodoflongevity AT lemstraafinaw nonsynonymousmutationinplcg2reducestheriskofalzheimersdiseasedementiawithlewybodiesandfrontotemporaldementiaandincreasesthelikelihoodoflongevity AT pijnenburgyolandeal nonsynonymousmutationinplcg2reducestheriskofalzheimersdiseasedementiawithlewybodiesandfrontotemporaldementiaandincreasesthelikelihoodoflongevity AT scheltensphilip nonsynonymousmutationinplcg2reducestheriskofalzheimersdiseasedementiawithlewybodiesandfrontotemporaldementiaandincreasesthelikelihoodoflongevity AT gasserthomas nonsynonymousmutationinplcg2reducestheriskofalzheimersdiseasedementiawithlewybodiesandfrontotemporaldementiaandincreasesthelikelihoodoflongevity AT chinnerypatrickf nonsynonymousmutationinplcg2reducestheriskofalzheimersdiseasedementiawithlewybodiesandfrontotemporaldementiaandincreasesthelikelihoodoflongevity AT hemmerbernhard nonsynonymousmutationinplcg2reducestheriskofalzheimersdiseasedementiawithlewybodiesandfrontotemporaldementiaandincreasesthelikelihoodoflongevity AT huismanmartijna nonsynonymousmutationinplcg2reducestheriskofalzheimersdiseasedementiawithlewybodiesandfrontotemporaldementiaandincreasesthelikelihoodoflongevity AT troncosojuan nonsynonymousmutationinplcg2reducestheriskofalzheimersdiseasedementiawithlewybodiesandfrontotemporaldementiaandincreasesthelikelihoodoflongevity AT morenofermin nonsynonymousmutationinplcg2reducestheriskofalzheimersdiseasedementiawithlewybodiesandfrontotemporaldementiaandincreasesthelikelihoodoflongevity AT nohrellena nonsynonymousmutationinplcg2reducestheriskofalzheimersdiseasedementiawithlewybodiesandfrontotemporaldementiaandincreasesthelikelihoodoflongevity AT sørensenthorkildia nonsynonymousmutationinplcg2reducestheriskofalzheimersdiseasedementiawithlewybodiesandfrontotemporaldementiaandincreasesthelikelihoodoflongevity AT heutinkpeter nonsynonymousmutationinplcg2reducestheriskofalzheimersdiseasedementiawithlewybodiesandfrontotemporaldementiaandincreasesthelikelihoodoflongevity AT sanchezjuanpascual nonsynonymousmutationinplcg2reducestheriskofalzheimersdiseasedementiawithlewybodiesandfrontotemporaldementiaandincreasesthelikelihoodoflongevity AT posthumadanielle nonsynonymousmutationinplcg2reducestheriskofalzheimersdiseasedementiawithlewybodiesandfrontotemporaldementiaandincreasesthelikelihoodoflongevity AT nonsynonymousmutationinplcg2reducestheriskofalzheimersdiseasedementiawithlewybodiesandfrontotemporaldementiaandincreasesthelikelihoodoflongevity AT clarimonjordi nonsynonymousmutationinplcg2reducestheriskofalzheimersdiseasedementiawithlewybodiesandfrontotemporaldementiaandincreasesthelikelihoodoflongevity AT christensenkaare nonsynonymousmutationinplcg2reducestheriskofalzheimersdiseasedementiawithlewybodiesandfrontotemporaldementiaandincreasesthelikelihoodoflongevity AT ertekintanernilufer nonsynonymousmutationinplcg2reducestheriskofalzheimersdiseasedementiawithlewybodiesandfrontotemporaldementiaandincreasesthelikelihoodoflongevity AT scholzsonjaw nonsynonymousmutationinplcg2reducestheriskofalzheimersdiseasedementiawithlewybodiesandfrontotemporaldementiaandincreasesthelikelihoodoflongevity AT ramirezalfredo nonsynonymousmutationinplcg2reducestheriskofalzheimersdiseasedementiawithlewybodiesandfrontotemporaldementiaandincreasesthelikelihoodoflongevity AT ruizagustin nonsynonymousmutationinplcg2reducestheriskofalzheimersdiseasedementiawithlewybodiesandfrontotemporaldementiaandincreasesthelikelihoodoflongevity AT slagboomeline nonsynonymousmutationinplcg2reducestheriskofalzheimersdiseasedementiawithlewybodiesandfrontotemporaldementiaandincreasesthelikelihoodoflongevity AT vanderflierwiesjem nonsynonymousmutationinplcg2reducestheriskofalzheimersdiseasedementiawithlewybodiesandfrontotemporaldementiaandincreasesthelikelihoodoflongevity AT holstegehenne nonsynonymousmutationinplcg2reducestheriskofalzheimersdiseasedementiawithlewybodiesandfrontotemporaldementiaandincreasesthelikelihoodoflongevity |