ArticleThe Journal of clinical investigation2020
Impact of TREM2R47H variant on tau pathology-induced gliosis and neurodegeneration.
Article in The Journal of clinical investigation, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 134 papers, 1 of them a synthesis that pooled it.
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Who cites it
134 citing papers in PubMed, 1 synthesis or guideline pooled it, 275 citations in OpenAlex.
- Gain-of-function Modulation of TREM2 and its Impact on Amyloid-β and Tau Pathologies in Alzheimer's Disease: A Systematic Review and Meta-analysis of Animal Studies.Molecular neurobiology · 2026Pooled it
- Preclinical and first-in-human evaluation of AL002, a novel TREM2 agonistic antibody for Alzheimer's disease.Alzheimer's research & therapy · 2024Trial
- Microglia in Perioperative Neurocognitive Disorders: Pathogenic Mechanisms and Emerging Concepts of Microglial Heterogeneity.Neurochemical research · 2026Review
- The Clearance-Centered Bottleneck in Alzheimer's Disease: From Coupled Glymphatic-Lymphatic Circuits to Therapeutic Opportunities.Molecular neurobiology · 2026Review
- TREM2 in neurodegenerative diseases and acute neurological injuries: mechanisms to targeted therapies.Cell communication and signaling : CCS · 2026Review
- Recent advances in Alzheimer's disease: From molecular mechanisms to therapeutic strategies.Cell · 2026Review
- Distinct factors drive the progression of tau pathology in Alzheimer's disease.Fundamental research · 2026Review
- Dietary Bioactives in Alzheimer's Disease: A Critical Appraisal of Clinical Trials and Future Nutritional Strategies.Nutrients · 2026Review
- InCytokine, an Open-Source Software, Reveals a TREM2 Variant-Specific Cytokine Signature.International journal of molecular sciences · 2026Article
- The gain-of-function TREM2-T96K mutation increases risk for Alzheimer's disease by impairing microglial function.Neuron · 2026Article
- GASDERMIN D-mediated pyroptosis as a therapeutic target in TAU-dependent frontotemporal dementia mouse model.Journal of biomedical science · 2026Article
- Perioperative neurocognitive disorders as a neuroimmune landscape disorder: microglial priming, state heterogeneity, and time-dependent neuroinflammation.Frontiers in immunology · 2026Review
- Roles of TREM2 in Alzheimer's disease.Translational neurodegeneration · 2025Review
- Disease-associated microglia in neurodegenerative diseases: Friend or foe?PLoS biology · 2025Review
- Cell autonomous microglia defects in a stem cell model of frontotemporal dementia tau.Molecular psychiatry · 2025Article
- Review
- TREM2 hit discovery using temperature-related intensity change (TRIC) technology: A proof-of-concept high-throughput screening approach.SLAS discovery : advancing life sciences R & D · 2025Article
- Hypercholesterolemia drives microglial dysfunction and weakens response to amyloid plaques.Experimental neurology · 2025Article
- Review
- Understanding the complex interplay between tau, amyloid and the network in the spatiotemporal progression of Alzheimer's disease.Progress in neurobiology · 2025Article
74 more citing papers are in PubMed but not listed here.
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Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
Abstract
Alzheimer's disease (AD) is characterized by plaques containing amyloid-β (Aβ) and neurofibrillary tangles composed of aggregated, hyperphosphorylated tau. Beyond tau and Aβ, evidence suggests that microglia play an important role in AD pathogenesis. Rare variants in the microglia-expressed triggering receptor expressed on myeloid cells 2 (TREM2) gene increase AD risk 2- to 4-fold. It is likely that these TREM2 variants increase AD risk by decreasing the response of microglia to Aβ and its local toxicity. However, neocortical Aβ pathology occurs many years before neocortical tau pathology in AD. Thus, it will be important to understand the role of TREM2 in the context of tauopathy. We investigated the impact of the AD-associated TREM2 variant (R47H) on tau-mediated neuropathology in the PS19 mouse model of tauopathy. We assessed PS19 mice expressing human TREM2CV (common variant) or human TREM2R47H. PS19-TREM2R47H mice had significantly attenuated brain atrophy and synapse loss versus PS19-TREM2CV mice. Gene expression analyses and CD68 immunostaining revealed attenuated microglial reactivity in PS19-TREM2R47H versus PS19-TREM2CV mice. There was also a decrease in phagocytosis of postsynaptic elements by microglia expressing TREM2R47H in the PS19 mice and in human AD brains. These findings suggest that impaired TREM2 signaling reduces microglia-mediated neurodegeneration in the setting of tauopathy.
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Registered trials
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.