PLCG2 protective variant p.P522R modulates tau pathology and disease progression in patients with mild cognitive impairment.

Aged Aged, 80 and over Alzheimer Disease / genetics Amyloid beta-Peptides / genetics Biomarkers / analysis Cognition / physiology Cognitive Dysfunction / genetics Disease Progression Female Humans Male Middle Aged Phospholipase C gamma / metabolism tau Proteins / cerebrospinal fluid
Alzheimer’s disease Cognitive decline Mild cognitive impairment PLCG2 Phospholipase C gamma 2

Journal

Acta neuropathologica
ISSN: 1432-0533
Titre abrégé: Acta Neuropathol
Pays: Germany
ID NLM: 0412041

Informations de publication

Date de publication:
06 2020
Historique:
received: 09 11 2019
accepted: 20 02 2020
revised: 19 02 2020
pubmed: 14 3 2020
medline: 9 6 2021
entrez: 14 3 2020
Statut: ppublish

Résumé

A rare coding variant (rs72824905, p.P522R) conferring protection against Alzheimer's disease (AD) was identified in the gene encoding the enzyme phospholipase-C-γ2 (PLCG2) that is highly expressed in microglia. To explore the protective nature of this variant, we employed latent process linear mixed models to examine the association of p.P522R with longitudinal cognitive decline in 3595 MCI patients, and in 10,097 individuals from population-based studies. Furthermore, association with CSF levels of pTau

Identifiants

DOI: 10.1007/s00401-020-02138-6 PMID: 32166339 PMC: PMC7244617
pubmed: 32166339
doi: 10.1007/s00401-020-02138-6
pii: 10.1007/s00401-020-02138-6
pmc: PMC7244617
doi:

Substances chimiques

Amyloid beta-Peptides 0
Biomarkers 0
tau Proteins 0
PLCG2 protein, human EC 3.1.4.3
Phospholipase C gamma EC 3.1.4.3

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S.

Langues

eng

Sous-ensembles de citation

IM

Pagination

1025-1044

Subventions

Organisme : NIA NIH HHS
ID : U01 AG024904
Pays : United States
Organisme : HSRD VA
ID : CDA 10-014
Pays : United States

Investigateurs

Luca Kleineidam (L)
Ilker Karaca (I)
Michael T Heneka (MT)
Wolfgang Maier (W)
Anja Schneider (A)
Michael Wagner (M)
Vincent Chouraki (V)
Phillipe Amouyel (P)
Jean-Charles Lambert (JC)
Tomasz Próchnicki (T)
Eicke Latz (E)
Sven J van der Lee (SJ)
Iris E Jansen (IE)
Marc Hulsman (M)
Philip Scheltens (P)
Wiesje M van der Flier (WM)
Henne Holstege (H)
Laura Madrid-Márquez (L)
Antonio González-Pérez (A)
Mª Eugenia Sáez (ME)
Holger Wagner-Thelen (H)
Pamela V Martino Adami (PV)
Frank Jessen (F)
Alfredo Ramirez (A)
Leonie Weinhold (L)
Matthias Schmid (M)
Steffen Wolfsgruber (S)
Frederic Brosseron (F)
Anne Boland (A)
Jean-Francois Deleuze (JF)
Piotr Lewczuk (P)
Johannes Kornhuber (J)
Julius Popp (J)
Oliver Peters (O)
Claudine Berr (C)
Reinhard Heun (R)
Lutz Frölich (L)
Christophe Tzourio (C)
Jean-François Dartigues (JF)
Michael Hüll (M)
Ana Espinosa (A)
Isabel Hernández (I)
Itziar de Rojas (I)
Adelina Orellana (A)
Sergi Valero (S)
Agustin Ruiz (A)
Lluis Tarraga (L)
Merce Boada (M)
Najada Stringa (N)
Natasja M van Schoor (NM)
Martijn Huisman (M)
Eckart Rüther (E)
Jens Wiltfang (J)
Martin Scherer (M)
Steffi Riedel-Heller (S)

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Auteurs

Luca Kleineidam (L)

Department of Neurodegenerative Diseases and Geriatric Psychiatry, University Hospital Bonn, Bonn, Germany.
Division of Neurogenetics and Molecular Psychiatry, Department of Psychiatry and Psychotherapy, Medical Faculty, University of Cologne, Cologne, Germany.
German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany.

Vincent Chouraki (V)

Univ. Lille, Inserm, CHU Lille, Institut Pasteur de Lille, U1167-RID-AGE-Facteurs de risque Et déterminants moléculaires des maladies liées au vieillissement, Lille, France.
Epidemiology and Public Health Department, Centre Hospitalier Universitaire de Lille, Lille, France.

Tomasz Próchnicki (T)

Institute of Innate Immunity, University Hospitals Bonn, Bonn, Germany.

Sven J van der Lee (SJ)

Department of Neurology, Alzheimer Center Amsterdam, Amsterdam Neuroscience, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
Department of Clinical Genetics, Amsterdam Neuroscience, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.

Laura Madrid-Márquez (L)

Andalusian Bioinformatics Research Centre (CAEBi), Seville, Spain.

Holger Wagner-Thelen (H)

Department of Neurodegenerative Diseases and Geriatric Psychiatry, University Hospital Bonn, Bonn, Germany.
Division of Neurogenetics and Molecular Psychiatry, Department of Psychiatry and Psychotherapy, Medical Faculty, University of Cologne, Cologne, Germany.

Ilker Karaca (I)

Department of Neurodegenerative Diseases and Geriatric Psychiatry, University Hospital Bonn, Bonn, Germany.

Leonie Weinhold (L)

Institute of Medical Biometry, Informatics and Epidemiology, University Hospital of Bonn, Bonn, Germany.

Steffen Wolfsgruber (S)

Department of Neurodegenerative Diseases and Geriatric Psychiatry, University Hospital Bonn, Bonn, Germany.
German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany.

Anne Boland (A)

Centre National de Recherche en Génomique Humaine (CNRGH), Institut de Biologie François Jacob, CEA, Université Paris-Saclay, Évry, France.

Pamela V Martino Adami (PV)

Division of Neurogenetics and Molecular Psychiatry, Department of Psychiatry and Psychotherapy, Medical Faculty, University of Cologne, Cologne, Germany.

Piotr Lewczuk (P)

Department of Psychiatry and Psychotherapy, Universitätsklinikum Erlangen, and Friedrich-Alexander Universität Erlangen-Nürnberg, Erlangen, Germany.
Department of Neurodegeneration Diagnostics, Medical University of Białystok, Białystok, Poland.
Department of Biochemical Diagnostics, University Hospital of Białystok, Białystok, Poland.

Julius Popp (J)

Department of Psychiatry, Lausanne University Hospital, Prilly, Switzerland.
Department of Geriatric Psychiatry, University Hospital of Psychiatry Zurich, Zurich, Switzerland.

Frederic Brosseron (F)

Department of Neurodegenerative Diseases and Geriatric Psychiatry, University Hospital Bonn, Bonn, Germany.
German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany.

Iris E Jansen (IE)

Department of Neurology, Alzheimer Center Amsterdam, Amsterdam Neuroscience, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
Department of Complex Trait Genetics, Center for Neurogenomics and Cognitive Research, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.

Marc Hulsman (M)

Department of Neurology, Alzheimer Center Amsterdam, Amsterdam Neuroscience, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
Department of Clinical Genetics, Amsterdam Neuroscience, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.

Johannes Kornhuber (J)

Department of Psychiatry and Psychotherapy, Universitätsklinikum Erlangen, and Friedrich-Alexander Universität Erlangen-Nürnberg, Erlangen, Germany.

Oliver Peters (O)

Department of Psychiatry, Charité - Universitätsmedizin Berlin, Berlin, Germany.
DZNE, German Center for Neurodegenerative Diseases, Berlin, Germany.

Claudine Berr (C)

INSERM, University Montpellier, Neuropsychiatry: Epidemiological and Clinical Research, Montpellier, France.

Reinhard Heun (R)

Department of Psychiatry and Psychotherapy, University Hospital Bonn, 53127, Bonn, Germany.

Lutz Frölich (L)

Department of Geriatric Psychiatry, Medical Faculty Mannheim, Central Institute of Mental Health, University of Heidelberg, Mannheim, Germany.

Christophe Tzourio (C)

Inserm, Bordeaux Population Health Research Center, UMR1219, University of Bordeaux, Bordeaux, France.

Jean-François Dartigues (JF)

Inserm, Bordeaux Population Health Research Center, UMR1219, University of Bordeaux, Bordeaux, France.

Michael Hüll (M)

Department of Psychiatry and Psychotherapy, Center for Psychiatry, Clinic for Geriatric Psychiatry and Psychotherapy Emmendingen, University of Freiburg, Freiburg, Germany.

Ana Espinosa (A)

Research Center and Memory Clinic, Fundació ACE, Institut Català de Neurociències Aplicades-Universitat Internacional de Catalunya-Barcelona, Barcelona, Spain.
Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Instituto de Salud Carlos III, Madrid, Spain.

Isabel Hernández (I)

Research Center and Memory Clinic, Fundació ACE, Institut Català de Neurociències Aplicades-Universitat Internacional de Catalunya-Barcelona, Barcelona, Spain.
Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Instituto de Salud Carlos III, Madrid, Spain.

Itziar de Rojas (I)

Research Center and Memory Clinic, Fundació ACE, Institut Català de Neurociències Aplicades-Universitat Internacional de Catalunya-Barcelona, Barcelona, Spain.
Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Instituto de Salud Carlos III, Madrid, Spain.

Adelina Orellana (A)

Research Center and Memory Clinic, Fundació ACE, Institut Català de Neurociències Aplicades-Universitat Internacional de Catalunya-Barcelona, Barcelona, Spain.

Sergi Valero (S)

Research Center and Memory Clinic, Fundació ACE, Institut Català de Neurociències Aplicades-Universitat Internacional de Catalunya-Barcelona, Barcelona, Spain.
Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Instituto de Salud Carlos III, Madrid, Spain.

Najada Stringa (N)

Department of Epidemiology and Biostatistics, Amsterdam Public Health Research Institute, Amsterdam UMC-Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.

Natasja M van Schoor (NM)

Department of Epidemiology and Biostatistics, Amsterdam Public Health Research Institute, Amsterdam UMC-Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.

Martijn Huisman (M)

Department of Epidemiology and Biostatistics, Amsterdam Public Health Research Institute, Amsterdam UMC-Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.

Philip Scheltens (P)

Department of Neurology, Alzheimer Center Amsterdam, Amsterdam Neuroscience, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.

Eckart Rüther (E)

Department of Psychiatry and Psychotherapy, University Medical Center Göttingen, Göttingen, Germany.

Jean-Francois Deleuze (JF)

Centre National de Recherche en Génomique Humaine (CNRGH), Institut de Biologie François Jacob, CEA, Université Paris-Saclay, Évry, France.

Jens Wiltfang (J)

Department of Psychiatry and Psychotherapy, University Medical Center Göttingen, Göttingen, Germany.
German Center for Neurodegenerative Diseases (DZNE), Göttingen, Germany.
iBiMED, Medical Sciences Department, University of Aveiro, Aveiro, Portugal.

Lluis Tarraga (L)

Research Center and Memory Clinic, Fundació ACE, Institut Català de Neurociències Aplicades-Universitat Internacional de Catalunya-Barcelona, Barcelona, Spain.
Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Instituto de Salud Carlos III, Madrid, Spain.

Matthias Schmid (M)

German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany.
Institute of Medical Biometry, Informatics and Epidemiology, University Hospital of Bonn, Bonn, Germany.

Martin Scherer (M)

Department of Primary Medical Care, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

Steffi Riedel-Heller (S)

Institute of Social Medicine, Occupational Health and Public Health, University of Leipzig, Leipzig, Germany.

Michael T Heneka (MT)

Department of Neurodegenerative Diseases and Geriatric Psychiatry, University Hospital Bonn, Bonn, Germany.
German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany.
Division of Infectious Diseases and Immunology, Department of Medicine, University of Massachusetts Medical School, Worcester, MA, USA.

Philippe Amouyel (P)

Univ. Lille, Inserm, CHU Lille, Institut Pasteur de Lille, U1167-RID-AGE-Facteurs de risque Et déterminants moléculaires des maladies liées au vieillissement, Lille, France.

Frank Jessen (F)

German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany.
Department of Psychiatry and Psychotherapy, Medical Faculty, University of Cologne, Cologne, Germany.

Merce Boada (M)

Research Center and Memory Clinic, Fundació ACE, Institut Català de Neurociències Aplicades-Universitat Internacional de Catalunya-Barcelona, Barcelona, Spain.
Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Instituto de Salud Carlos III, Madrid, Spain.

Wolfgang Maier (W)

Department of Neurodegenerative Diseases and Geriatric Psychiatry, University Hospital Bonn, Bonn, Germany.
German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany.

Anja Schneider (A)

Department of Neurodegenerative Diseases and Geriatric Psychiatry, University Hospital Bonn, Bonn, Germany.
German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany.

Antonio González-Pérez (A)

Andalusian Bioinformatics Research Centre (CAEBi), Seville, Spain.

Wiesje M van der Flier (WM)

Department of Neurology, Alzheimer Center Amsterdam, Amsterdam Neuroscience, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.

Michael Wagner (M)

Department of Neurodegenerative Diseases and Geriatric Psychiatry, University Hospital Bonn, Bonn, Germany.
German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany.

Jean-Charles Lambert (JC)

Univ. Lille, Inserm, CHU Lille, Institut Pasteur de Lille, U1167-RID-AGE-Facteurs de risque Et déterminants moléculaires des maladies liées au vieillissement, Lille, France.

Henne Holstege (H)

Department of Neurology, Alzheimer Center Amsterdam, Amsterdam Neuroscience, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
Department of Clinical Genetics, Amsterdam Neuroscience, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.

Mª Eugenia Sáez (ME)

Andalusian Bioinformatics Research Centre (CAEBi), Seville, Spain.

Eicke Latz (E)

German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany.
Institute of Innate Immunity, University Hospitals Bonn, Bonn, Germany.
Division of Infectious Diseases and Immunology, Department of Medicine, University of Massachusetts Medical School, Worcester, MA, USA.
Centre for Molecular Inflammation Research (CEMIR), Norwegian University of Science and Technology, Trondheim, Norway.

Agustin Ruiz (A)

Research Center and Memory Clinic, Fundació ACE, Institut Català de Neurociències Aplicades-Universitat Internacional de Catalunya-Barcelona, Barcelona, Spain.
Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Instituto de Salud Carlos III, Madrid, Spain.

Alfredo Ramirez (A)

Department of Neurodegenerative Diseases and Geriatric Psychiatry, University Hospital Bonn, Bonn, Germany. alfredo.ramirez@uk-koeln.de.
Division of Neurogenetics and Molecular Psychiatry, Department of Psychiatry and Psychotherapy, Medical Faculty, University of Cologne, Cologne, Germany. alfredo.ramirez@uk-koeln.de.
ORCID: 0000-0003-4991-763X

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Classifications MeSH

questionsmedicales.fr › Personnes › Tranches d'âge › Adulte › Sujet âgé › PLCG2 protective variant p.P522R modulates tau...
questionsmedicales.fr › Personnes › Tranches d'âge › Adulte › Sujet âgé › Sujet âgé de 80 ans ou plus › PLCG2 protective variant p.P522R modulates tau...
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questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines membranaires › Peptides bêta-amyloïdes › PLCG2 protective variant p.P522R modulates tau...
questionsmedicales.fr › Facteurs biologiques › Marqueurs biologiques › PLCG2 protective variant p.P522R modulates tau...
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questionsmedicales.fr › Troubles mentaux › Troubles neurocognitifs › Troubles de la cognition › Dysfonctionnement cognitif › PLCG2 protective variant p.P522R modulates tau...
questionsmedicales.fr › États, signes et symptômes pathologiques › Processus pathologiques › Caractéristiques de la maladie › Évolution de la maladie › PLCG2 protective variant p.P522R modulates tau...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › PLCG2 protective variant p.P522R modulates tau...
questionsmedicales.fr › Personnes › Tranches d'âge › Adulte › Adulte d'âge moyen › PLCG2 protective variant p.P522R modulates tau...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines et peptides de signalisation intracellulaire › Phosphoinositide Phospholipase C › Phospholipase C gamma › PLCG2 protective variant p.P522R modulates tau...
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