ArticleActa neuropathologica2020
PLCG2 protective variant p.P522R modulates tau pathology and disease progression in patients with mild cognitive impairment.
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Article in Acta neuropathologica, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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41 citing papers in PubMed, 71 citations in OpenAlex.
- PLCG2 downregulation impairs synaptic function and increases Alzheimer's disease hallmarks in neuronal cultures.Nature genetics · 2026Article
- PLCγ2 deficiency compromises systemic immune tolerance and erodes myelin homeostasis while enhancing oxidative metabolism in the mouse brain.bioRxiv : the preprint server for biology · 2026Article
- Non-microglial downregulation ofbioRxiv : the preprint server for biology · 2026Article
- PLCG2 signaling and genetic resilience in Alzheimer's disease.Molecular neurodegeneration · 2026Review
- Immune dysfunction in Alzheimer disease.Nature reviews. Neuroscience · 2026Review
- PLCG2 across human disease: genetic variants, signaling mechanisms, and clinical implications.Journal of translational medicine · 2026Review
- Genetics of PLCG2 expression and splicing relative to Alzheimer's disease risk.Molecular neurodegeneration advances · 2026Article
- Microglial phagocytosis in Alzheimer disease.Nature reviews. Neurology · 2026Review
- Alzheimer's disease polygenic risk score associates with hippocampal subfield atrophy and immune-related genetic mechanism.Frontiers in aging neuroscience · 2026Article
- Protective genetic variants against Alzheimer's disease.The Lancet. Neurology · 2025Review
- X-chromosome-wide association study for Alzheimer's disease.Molecular psychiatry · 2025Article
- PLCG2 modulates TREM2 expression and signaling in response to Alzheimer's disease pathology.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Neuroinflammation in Alzheimer disease.Nature reviews. Immunology · 2025Review
- The protective PLCγ2-P522R variant mitigates Alzheimer's disease-associated pathologies by enhancing beneficial microglial functions.Journal of neuroinflammation · 2025Article
- The crystal and cryo-EM structures of PLCγ2 reveal dynamic interdomain recognitions in autoinhibition.Science advances · 2024Article
- Alzheimer's disease-associated protective variant Plcg2-P522R modulates peripheral macrophage function in a sex-dimorphic manner.Journal of neuroinflammation · 2024Article
- Multi-omics analyses reveal novel effects of PLCγ2 deficiency in the mouse brain.bioRxiv : the preprint server for biology · 2023Article
- Article
- Step by step: towards a better understanding of the genetic architecture of Alzheimer's disease.Molecular psychiatry · 2023Review
- A novel fluorogenic reporter substrate for 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2 (PLCγ2): Application to high-throughput screening for activators to treat Alzheimer's disease.SLAS discovery : advancing life sciences R & D · 2023Article
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Authors and funding
56 authors at 20 institutions in 10 countries.
Luca KleineidamDepartment of Neurodegenerative Diseases and Geriatric Psychiatry, University Hospital Bonn, Bonn, Germany.
Vincent ChourakiUniv. Lille, Inserm, CHU Lille, Institut Pasteur de Lille, U1167-RID-AGE-Facteurs de risque Et déterminants moléculaires des maladies liées au vieillissement, Lille, France.
Tomasz PróchnickiInstitute of Innate Immunity, University Hospitals Bonn, Bonn, Germany.
Sven J van der LeeDepartment of Neurology, Alzheimer Center Amsterdam, Amsterdam Neuroscience, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
Laura Madrid-MárquezAndalusian Bioinformatics Research Centre (CAEBi), Seville, Spain.
Holger Wagner-ThelenDepartment of Neurodegenerative Diseases and Geriatric Psychiatry, University Hospital Bonn, Bonn, Germany.
Ilker KaracaDepartment of Neurodegenerative Diseases and Geriatric Psychiatry, University Hospital Bonn, Bonn, Germany.
Leonie WeinholdInstitute of Medical Biometry, Informatics and Epidemiology, University Hospital of Bonn, Bonn, Germany.
Steffen WolfsgruberDepartment of Neurodegenerative Diseases and Geriatric Psychiatry, University Hospital Bonn, Bonn, Germany.
Anne BolandCentre National de Recherche en Génomique Humaine (CNRGH), Institut de Biologie François Jacob, CEA, Université Paris-Saclay, Évry, France.
Pamela V Martino AdamiDivision of Neurogenetics and Molecular Psychiatry, Department of Psychiatry and Psychotherapy, Medical Faculty, University of Cologne, Cologne, Germany.
Piotr LewczukDepartment of Psychiatry and Psychotherapy, Universitätsklinikum Erlangen, and Friedrich-Alexander Universität Erlangen-Nürnberg, Erlangen, Germany.
Julius PoppDepartment of Psychiatry, Lausanne University Hospital, Prilly, Switzerland.
Frederic BrosseronDepartment of Neurodegenerative Diseases and Geriatric Psychiatry, University Hospital Bonn, Bonn, Germany.
Iris E JansenDepartment of Neurology, Alzheimer Center Amsterdam, Amsterdam Neuroscience, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
Marc HulsmanDepartment of Neurology, Alzheimer Center Amsterdam, Amsterdam Neuroscience, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
Johannes KornhuberDepartment of Psychiatry and Psychotherapy, Universitätsklinikum Erlangen, and Friedrich-Alexander Universität Erlangen-Nürnberg, Erlangen, Germany.
Oliver PetersDepartment of Psychiatry, Charité - Universitätsmedizin Berlin, Berlin, Germany.
Claudine BerrINSERM, University Montpellier, Neuropsychiatry: Epidemiological and Clinical Research, Montpellier, France.
Reinhard HeunDepartment of Psychiatry and Psychotherapy, University Hospital Bonn, 53127, Bonn, Germany.
Lutz FrölichDepartment of Geriatric Psychiatry, Medical Faculty Mannheim, Central Institute of Mental Health, University of Heidelberg, Mannheim, Germany.
Christophe TzourioInserm, Bordeaux Population Health Research Center, UMR1219, University of Bordeaux, Bordeaux, France.
Jean-François DartiguesInserm, Bordeaux Population Health Research Center, UMR1219, University of Bordeaux, Bordeaux, France.
Michael HüllDepartment of Psychiatry and Psychotherapy, Center for Psychiatry, Clinic for Geriatric Psychiatry and Psychotherapy Emmendingen, University of Freiburg, Freiburg, Germany.
Ana EspinosaResearch Center and Memory Clinic, Fundació ACE, Institut Català de Neurociències Aplicades-Universitat Internacional de Catalunya-Barcelona, Barcelona, Spain.
Isabel HernándezResearch Center and Memory Clinic, Fundació ACE, Institut Català de Neurociències Aplicades-Universitat Internacional de Catalunya-Barcelona, Barcelona, Spain.
Itziar de RojasResearch Center and Memory Clinic, Fundació ACE, Institut Català de Neurociències Aplicades-Universitat Internacional de Catalunya-Barcelona, Barcelona, Spain.
Adelina OrellanaResearch Center and Memory Clinic, Fundació ACE, Institut Català de Neurociències Aplicades-Universitat Internacional de Catalunya-Barcelona, Barcelona, Spain.
Sergi ValeroResearch Center and Memory Clinic, Fundació ACE, Institut Català de Neurociències Aplicades-Universitat Internacional de Catalunya-Barcelona, Barcelona, Spain.
Najada StringaDepartment of Epidemiology and Biostatistics, Amsterdam Public Health Research Institute, Amsterdam UMC-Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
Natasja M van SchoorDepartment of Epidemiology and Biostatistics, Amsterdam Public Health Research Institute, Amsterdam UMC-Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
Martijn HuismanDepartment of Epidemiology and Biostatistics, Amsterdam Public Health Research Institute, Amsterdam UMC-Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
Philip ScheltensDepartment of Neurology, Alzheimer Center Amsterdam, Amsterdam Neuroscience, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
Alzheimer’s Disease Neuroimaging Initiative (ADNI)
Eckart RütherDepartment of Psychiatry and Psychotherapy, University Medical Center Göttingen, Göttingen, Germany.
Jean-Francois DeleuzeCentre National de Recherche en Génomique Humaine (CNRGH), Institut de Biologie François Jacob, CEA, Université Paris-Saclay, Évry, France.
Jens WiltfangDepartment of Psychiatry and Psychotherapy, University Medical Center Göttingen, Göttingen, Germany.
Lluis TarragaResearch Center and Memory Clinic, Fundació ACE, Institut Català de Neurociències Aplicades-Universitat Internacional de Catalunya-Barcelona, Barcelona, Spain.
Matthias SchmidGerman Center for Neurodegenerative Diseases (DZNE), Bonn, Germany.
Martin SchererDepartment of Primary Medical Care, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Steffi Riedel-HellerInstitute of Social Medicine, Occupational Health and Public Health, University of Leipzig, Leipzig, Germany.
Michael T HenekaDepartment of Neurodegenerative Diseases and Geriatric Psychiatry, University Hospital Bonn, Bonn, Germany.
Philippe AmouyelUniv. 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 JessenGerman Center for Neurodegenerative Diseases (DZNE), Bonn, Germany.
Merce BoadaResearch Center and Memory Clinic, Fundació ACE, Institut Català de Neurociències Aplicades-Universitat Internacional de Catalunya-Barcelona, Barcelona, Spain.
Wolfgang MaierDepartment of Neurodegenerative Diseases and Geriatric Psychiatry, University Hospital Bonn, Bonn, Germany.
Anja SchneiderDepartment of Neurodegenerative Diseases and Geriatric Psychiatry, University Hospital Bonn, Bonn, Germany.
Antonio González-PérezAndalusian Bioinformatics Research Centre (CAEBi), Seville, Spain.
Wiesje M van der FlierDepartment of Neurology, Alzheimer Center Amsterdam, Amsterdam Neuroscience, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
Michael WagnerDepartment of Neurodegenerative Diseases and Geriatric Psychiatry, University Hospital Bonn, Bonn, Germany.
Jean-Charles LambertUniv. 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 HolstegeDepartment of Neurology, Alzheimer Center Amsterdam, Amsterdam Neuroscience, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
Mª Eugenia SáezAndalusian Bioinformatics Research Centre (CAEBi), Seville, Spain.
Eicke LatzGerman Center for Neurodegenerative Diseases (DZNE), Bonn, Germany.
Agustin Ruiz *Research Center and Memory Clinic, Fundació ACE, Institut Català de Neurociències Aplicades-Universitat Internacional de Catalunya-Barcelona, Barcelona, Spain.
Alfredo Ramirez *Department of Neurodegenerative Diseases and Geriatric Psychiatry, University Hospital Bonn, Bonn, Germany. alfredo.ramirez@uk-koeln.de.ORCID http://orcid.org/0000-0003-4991-763X
University Hospital Bonn · DEInstituto de Salud Carlos III · ESAmsterdam Neuroscience · NLUniversity of Cologne · DEInserm · FRAmsterdam University Medical Centers · NLCentro Andaluz de Biología del Desarrollo · ESCommissariat à l'Énergie Atomique et aux Énergies Alternatives · FRGerman Center for Neurodegenerative Diseases · DEUniversité de Bordeaux · FRUniversity of Massachusetts Chan Medical School · USFriedrich-Alexander-Universität Erlangen-Nürnberg · DEHeidelberg University · DELeipzig University · DEMedical University of Białystok · PLUniversität Hamburg · DEUniversitat Internacional de Catalunya · ESUniversitätsmedizin Göttingen · DEUniversity Hospital of Lausanne · CHUniversity of Freiburg · DE
Funding
Alzheimer's Disease Neuroimaging Initiative - SupplementU01AG024904 · NIA · NORTHERN CALIFORNIA INSTITUTE RES &EDUC · PI WEINER, MICHAEL W · 2004 to 2015
$121.0MHSRD VA CDA 10-014NIA NIH HHS U01 AG024904
Abstract
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
Indexed as
AgedAged, 80 and overAlzheimer DiseaseAmyloid beta-PeptidesBiomarkersCognitionCognitive DysfunctionDisease ProgressionFemaleHumansMaleMiddle AgedPhospholipase C gammatau ProteinsAmyloid beta-PeptidesBiomarkersPhospholipase C gammaPLCG2 protein, humantau ProteinsAlzheimer’s diseaseCognitive declineMild cognitive impairmentPhospholipase C gamma 2PLCG2
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