ArticleGenome medicine2023
TREM2 splice isoforms generate soluble TREM2 species that disrupt long-term potentiation.
Article in Genome medicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers, 1 of them a synthesis that pooled it.
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Who cites it
30 citing papers in PubMed, 1 synthesis or guideline pooled it, 40 citations in OpenAlex.
- Pooled it
- Uncovering the biological mechanisms of TREM2 with molecular simulations: A comprehensive review and perspective.Progress in biophysics and molecular biology · 2026Review
- PLCG2 signaling and genetic resilience in Alzheimer's disease.Molecular neurodegeneration · 2026Review
- Ethanol induces neuroimmune dysregulation and soluble TREM2 generation in a human iPSC neuron, astrocyte, microglia triculture model.Alcohol (Fayetteville, N.Y.) · 2026Article
- HMC3 revealed: how much do these "Microglia" really tell us?Frontiers in immunology · 2026Review
- Nutritional substrates and microglial metabolic fitness in brain aging and Alzheimer's disease: from lipid handling to TREM2-linked translation.Frontiers in nutrition · 2026Review
- TREM2 as a central immunometabolic hub in Alzheimer's disease: linking microglial states, lipid stress, and disease-stage-specific intervention.Frontiers in immunology · 2026Review
- Soluble Triggering Receptor Expressed on Myeloid Cells 2 is a Biomarker but Not a Mediator of Fibrosing Steatohepatitis.Gastro hep advances · 2026Article
- Mechanistic Disruption of the TREM2-DAP12 Transmembrane Complex by Alzheimer's Disease Mutations: A Multiscale Simulation Study.Journal of chemical information and modeling · 2025Article
- The Role of TREM2 After Stroke: From Mechanisms to Therapeutic Potential.Molecular neurobiology · 2025Review
- TREM2-driven peripheral macrophage regulation in inflammatory diseases: implications extending beyond neurological disorders.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2025Review
- Microglia-Mediated Phagocytosis in Alzheimer's Disease: Mechanisms, Heterogeneity, and Therapeutic Insights.Biomolecules · 2025Review
- TREM2-mediated regulation of myeloid cells in the tumor microenvironment: new insights and therapeutic prospects.NPJ precision oncology · 2025Review
- Roles of TREM2 in Alzheimer's disease.Translational neurodegeneration · 2025Review
- Is TREM2 a Stretch: Implications of TREM2 Along Spinal Cord Circuits in Health, Aging, Injury, and Disease.Cells · 2025Review
- Relationships of PGRN with sTREM2 in AD continuum and non-AD pathophysiology and their reciprocal roles in modulating amyloid pathology: two population-based study.Translational psychiatry · 2025Article
- The late-onset Alzheimer's disease risk factor RHBDF2 is a modifier of microglial TREM2 proteolysis.Life science alliance · 2025Article
- TREM2 and sTREM2 in Alzheimer's disease: from mechanisms to therapies.Molecular neurodegeneration · 2025Review
- Biophysical mapping of TREM2-ligand interactions reveals shared surfaces for engagement of multiple Alzheimer's disease ligands.Molecular neurodegeneration · 2025Article
- Microglial Modulation in Alzheimer's Disease: Central Players in Neuroinflammation and Pathogenesis.Current Alzheimer research · 2025Review
Corrections and comments
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Authors and funding
16 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundTREM2 is a transmembrane receptor expressed by myeloid cells and acts to regulate their immune response. TREM2 governs the response of microglia to amyloid and tau pathologies in the Alzheimer's disease (AD) brain. TREM2 is also present in a soluble form (sTREM2), and its CSF levels fluctuate as a function of AD progression. Analysis of stroke and AD mouse models revealed that sTREM2 proteins bind to neurons, which suggests sTREM2 may act in a non-cell autonomous manner to influence neuronal function. sTREM2 arises from the proteolytic cleavage of the membrane-associated receptor. However, alternatively spliced TREM2 species lacking a transmembrane domain have been postulated to contribute to the pool of sTREM2. Thus, both the source of sTREM2 species and its actions in the brain remain unclear.
methodsThe expression of TREM2 isoforms in the AD brain was assessed through the analysis of the Accelerating Medicines Partnership for Alzheimer's Disease Consortium transcriptomics data, as well as qPCR analysis using post-mortem samples of AD patients and of the AD mouse model 5xFAD. TREM2 cleavage and secretion were studied in vitro using HEK-293T and HMC3 cell lines. Synaptic plasticity, as evaluated by induction of LTP in hippocampal brain slices, was employed as a measure of sTREM2 actions.
resultsThree distinct TREM2 transcripts, namely ENST00000373113 (TREM2
conclusionsTREM2 transcripts can give rise to a heterogeneous pool of sTREM2 which acts to inhibit LTP. These results provide novel insight into the generation, regulation, and function of sTREM2 which fits into the complex biology of TREM2 and its role in human health and disease. Given that sTREM2 levels are linked to AD pathogenesis and progression, our finding that sTREM2 species interfere with LTP furthers our understanding about the role of TREM2 in AD.
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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.