ArticleNature neuroscience2020
Alzheimer's-associated PLCγ2 is a signaling node required for both TREM2 function and the inflammatory response in human microglia.
Article in Nature neuroscience, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 159 papers, 2 of them syntheses that pooled it.
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Who cites it
159 citing papers in PubMed, 2 syntheses or guidelines pooled it, 240 citations in OpenAlex.
- Transcriptional landscape of human microglia implicates age, sex, and APOE-related immunometabolic pathway perturbations.Aging cell · 2022Pooled it
- Targeting TREM2 for Parkinson's Disease: Where to Go?Frontiers in immunology · 2021Pooled it
- Article
- Microglia-Mediated Ependymal Injury in Bacille Calmette-Guérin-Induced Meningitis Is Attenuated by Sodium Butyrate with Restoration of Hmgcs2 Expression.Advances in respiratory medicine · 2026Article
- iPSC-Derived Microglia-like Cells Exhibit Protocol-Dependent Transcriptomic Features and Robust Phagocytosis of Glioma Cells.bioRxiv : the preprint server for biology · 2026Article
- TREM2 in neurodegenerative diseases and acute neurological injuries: mechanisms to targeted therapies.Cell communication and signaling : CCS · 2026Review
- 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
- Microglia and neuroinflammation: function, heterogeneity, and crosstalk.Cellular & molecular immunology · 2026Review
- Microglial ITAM & ITIM Signaling in Neurodegenerative Disease and Brain Aging.Journal of molecular biology · 2026Review
- Depletion of microglial compensation in glial network: Disease-associated response dynamics in the revised amyloid hypothesis.Neuroprotection (Chichester, England) · 2026Review
- Therapeutic targeting of neuroimmune mechanisms in neurodegeneration.Nature reviews. Drug discovery · 2026Review
- Dissecting microglial contributions to neurodegenerative disease pathophysiology using human pluripotent stem cells.Stem cell reports · 2026Review
- PLCG2 signaling and genetic resilience in Alzheimer's disease.Molecular neurodegeneration · 2026Review
- Age-related macular degeneration and cerebral amyloid angiopathy have similar pathologies from cholesterol-APOE-amyloid-β-complement mediated inflammation.Progress in retinal and eye research · 2026Review
- Comparative lipidomics of iPSC-derived microglia protocols reveal lipid droplet and immune differences mediated by media composition.Stem cell reports · 2026Article
- Protective PLCG2 variants associate with a delayed onset of Alzheimer's disease among heterozygous APOE ε4 carriers.Alzheimer's research & therapy · 2026Article
- TREM2 expression level is critical for microglial state, metabolic capacity and efficacy of TREM2 agonism.Nature communications · 2026Article
- PLCG2 across human disease: genetic variants, signaling mechanisms, and clinical implications.Journal of translational medicine · 2026Review
- Microglial Deletion of Hrh4 Alleviates Alzheimer's Disease Pathologies by Enhancing Microglial Phagocytosis of Amyloid-β and Tau.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- TREM2 as a central immunometabolic hub in Alzheimer's disease: linking microglial states, lipid stress, and disease-stage-specific intervention.Frontiers in immunology · 2026Review
99 more citing papers are in PubMed but not listed here.
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Authors and funding
14 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Human genetic data indicate that microglial dysfunction contributes to the pathology of Alzheimer's disease (AD), exemplified by the identification of coding variants in triggering receptor expressed on myeloid cells 2 (TREM2) and, more recently, in PLCG2, a phospholipase-encoding gene expressed in microglia. Although studies in mouse models have implicated specific Trem2-dependent microglial functions in AD, the underlying molecular mechanisms and translatability to human disease remain poorly defined. In this study, we used genetically engineered human induced pluripotent stem cell-derived microglia-like cells to show that TREM2 signals through PLCγ2 to mediate cell survival, phagocytosis, processing of neuronal debris, and lipid metabolism. Loss of TREM2 or PLCγ2 signaling leads to a shared signature of transcriptional dysregulation that underlies these phenotypes. Independent of TREM2, PLCγ2 also signals downstream of Toll-like receptors to mediate inflammatory responses. Therefore, PLCγ2 activity regulates divergent microglial functions via distinct TREM2-dependent and -independent signaling and might be involved in the transition to a microglial state associated with neurodegenerative disease.
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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 OpenQuestion graph.