ArticleImmunity2023
Genetic variants of phospholipase C-γ2 alter the phenotype and function of microglia and confer differential risk for Alzheimer's disease.
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Article in Immunity, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
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47citing papers in PubMed
7.9field-weighted citation impact, top 2% of its field
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Who cites it
47 citing papers in PubMed, 64 citations in OpenAlex.
- PLCG2 downregulation impairs synaptic function and increases Alzheimer's disease hallmarks in neuronal cultures.Nature genetics · 2026Article
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- 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
- Reshaping the immune landscape: next-generation microglia-targeted therapies for Alzheimer's disease.Biological research · 2026Review
- Microglial ITAM & ITIM Signaling in Neurodegenerative Disease and Brain Aging.Journal of molecular biology · 2026Review
- Therapeutic targeting of neuroimmune mechanisms in neurodegeneration.Nature reviews. Drug discovery · 2026Review
- Detecting Beta-Amyloid Plaque via Low Rank Based Orthogonal Projection and Spatial-Spectrum Detector Using High-Resolution Quantitative Susceptibility Mapping for Preclinical Studies.IEEE transactions on bio-medical engineering · 2026Article
- Abi3Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Simultaneous spatial transcriptomics and morphology profiling as tools to explore how microglia change with age.Nature aging · 2026Article
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- 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
- Systems biology of Alzheimer's Disease: a scoping review of key pathways and mechanisms.Molecular neurodegeneration · 2026Article
- Comparative lipidomics of iPSC-derived microglia protocols reveal lipid droplet and immune differences mediated by media composition.Stem cell reports · 2026Article
- Targeting immune cells in the aged brain reveals that engineered cytokine IL-10 enhances neurogenesis and improves cognition.Immunity · 2026Article
- Protective PLCG2 variants associate with a delayed onset of Alzheimer's disease among heterozygous APOE ε4 carriers.Alzheimer's research & therapy · 2026Article
- PLCG2 across human disease: genetic variants, signaling mechanisms, and clinical implications.Journal of translational medicine · 2026Review
- Differential downstream signaling in microglia lacking Alzheimer's-related TREM2 or its adaptor TYROBP/DAP12.Molecular neurodegeneration advances · 2026Article
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Authors and funding
25 authors at 5 institutions in 1 country.
Andy P TsaiStark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, IN, USA; Wu Tsai Neurosciences Institute, Stanford University School of Medicine, Stanford, CA, USA.
Chuanpeng DongDepartment of Medical and Molecular Genetics, Center for Computational Biology and Bioinformatics, Indiana University School of Medicine, Indianapolis, IN, USA; Department of Genetics, Yale University School of Medicine, New Haven, CT, USA.
Peter Bor-Chian LinStark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, IN, USA.
Adrian L OblakStark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, IN, USA; Department of Radiology & Imaging Sciences, Indiana University School of Medicine, Indianapolis, IN, USA.
Gonzalo Viana Di PriscoStark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, IN, USA; Department of Pharmacology and Toxicology, Indiana University School of Medicine, Indianapolis, IN, USA.
Nian WangStark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, IN, USA; Department of Radiology & Imaging Sciences, Indiana University School of Medicine, Indianapolis, IN, USA.
Nicole HajicekDepartment of Pharmacology, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Adam J CarrDivision of Chemical Biology and Medicinal Chemistry, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Emma K LendyDepartment of Biochemistry, Purdue University, West Lafayette, IN, USA.
Oliver HahnWu Tsai Neurosciences Institute, Stanford University School of Medicine, Stanford, CA, USA.
Micaiah AtkinsWu Tsai Neurosciences Institute, Stanford University School of Medicine, Stanford, CA, USA.
Aulden G FoltzWu Tsai Neurosciences Institute, Stanford University School of Medicine, Stanford, CA, USA.
Jheel PatelStark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, IN, USA.
Guixiang XuStark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, IN, USA.
Miguel MoutinhoStark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, IN, USA.
John SondekDepartment of Pharmacology, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Qisheng ZhangDepartment of Pharmacology, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; Division of Chemical Biology and Medicinal Chemistry, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Andrew D MesecarDepartment of Biochemistry, Purdue University, West Lafayette, IN, USA.
Yunlong LiuDepartment of Medical and Molecular Genetics, Center for Computational Biology and Bioinformatics, Indiana University School of Medicine, Indianapolis, IN, USA.
Brady K AtwoodStark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, IN, USA; Department of Pharmacology and Toxicology, Indiana University School of Medicine, Indianapolis, IN, USA.
Tony Wyss-CorayWu Tsai Neurosciences Institute, Stanford University School of Medicine, Stanford, CA, USA.
Kwangsik NhoDepartment of Radiology & Imaging Sciences, Indiana University School of Medicine, Indianapolis, IN, USA.
Stephanie J BisselStark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, IN, USA; Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, USA.
Bruce T LambStark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, IN, USA; Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, USA.
Gary E LandrethStark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, IN, USA; Department of Anatomy, Cell Biology and Physiology, Indiana University School of Medicine, Indianapolis, IN, USA. Electronic address: glandret@iu.edu.
Indiana University School of MedicineNeurosciences Institute · USUniversity of North Carolina at Chapel Hill · USPurdue University West Lafayette · USYale University · US
Funding
The IU/JAX Alzheimer's Disease Precision Models Center: Rat F344U54AG054345 · NIA · INDIANA UNIVERSITY INDIANAPOLIS · PI Gregory W Carter · 2016 to 2026
$95.6MImpact of PLCG2 Alzheimer's Disease Risk Variants on Microglia Biology and Disease PathogenesisRF1AG074566 · NIA · INDIANA UNIVERSITY INDIANAPOLIS · PI BISSEL, STEPHANIE J, LAMB, BRUCE T · 2021 to 2021
$2.3MCharacterization of Whole Brain Demyelination and Axon Damage Using High-resolution Magnetic Resonance ImagingR01NS125020 · NINDS · UT SOUTHWESTERN MEDICAL CENTER · PI Nian Wang · 2022 to 2026
$2.0MIntegrating Neuroimaging, Multi-omics, and Clinical Data in Complex DiseaseR01LM012535 · NLM · INDIANA UNIVERSITY INDIANAPOLIS · PI NHO, KWANGSIK TIMOTHY · 2017 to 2021
$1.7MPhospholipase C IsozymesR35GM149299 · NIGMS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI JOHN E SONDEK · 2023 to 2026
$1.7MImpact of PLCG2 Alzheimer's Disease Risk Variants on Microglia Biology and Disease PathogenesisR01AG074566 · NIA · INDIANA UNIVERSITY INDIANAPOLIS · PI BISSEL, STEPHANIE J, LAMB, BRUCE T · 2024 to 2025
$1.5MIn vivo assessment of the role of neurons and glia in tau propagationK01AG054753 · NIA · INDIANA UNIVERSITY INDIANAPOLIS · PI OBLAK, ADRIAN LYNN · 2017 to 2021
$625kIntegrative analysis of alternative splicing in Alzheimer's diseaseR03AG063250 · NIA · UNIVERSITY OF UTAH · PI LEE, YOUNGHEE · 2019 to 2020
$323kNIA NIH HHS K01 AG054753NIA NIH HHS R01 AG074566NIA NIH HHS R03 AG063250NIA NIH HHS RF1 AG074566NIA NIH HHS U54 AG054345NIGMS NIH HHS R35 GM149299NINDS NIH HHS R01 NS125020NLM NIH HHS R01 LM012535
Abstract
Genetic association studies have demonstrated the critical involvement of the microglial immune response in Alzheimer's disease (AD) pathogenesis. Phospholipase C-gamma-2 (PLCG2) is selectively expressed by microglia and functions in many immune receptor signaling pathways. In AD, PLCG2 is induced uniquely in plaque-associated microglia. A genetic variant of PLCG2, PLCG2
Indexed as
Alzheimer DiseasePhospholipase C gammaAnimalsGenetic Association StudiesMiceMicrogliaPhagocytosisPhenotypePlaque, AmyloidPhospholipase C gammaPlcg2 protein, mouseAlzheimer’s diseaseamyloid pathologymicrogliamicroglial uptake capacitymicroglia-plaque interactionsneuroinflammationP522R and M28L variantphospholipase C-gamma-2synaptic functiontranscriptional programs
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.