ArticleNature communications2026
TREM2 expression level is critical for microglial state, metabolic capacity and efficacy of TREM2 agonism.
Article in Nature communications, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
19 citing papers in PubMed.
- A high-throughput method to computationally develop candidate adverse outcome pathways in humans: a proof of concept with insecticides and Parkinson's Disease.Toxicological sciences : an official journal of the Society of Toxicology · 2026Article
- Pharmacological modulation of cGAS-STING-NLRP3 signaling by nano-immunomodulators in Alzheimer and Parkinson disease.Inflammopharmacology · 2026Review
- TMEM59 regulates microglial Aβ phagocytosis in a TREM2-dependent manner and acts as a potential therapeutic target for Aβ amyloidosis.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Tissue-Resident Macrophage in Inflammation and Cancer.MedComm · 2026Review
- Modeling stimulus-induced stress responses in microglia-like cells using a commercial iPSC-dCas9-KRAB line.Stem cell research · 2026Article
- Microglial mitophagy as an immunometabolic checkpoint in alzheimer's disease: linking mitochondrial quality control to neuroinflammation.Journal of neuroinflammation · 2026Review
- Recent advances in Alzheimer's disease: From molecular mechanisms to therapeutic strategies.Cell · 2026Review
- Review
- Lymphoid-like Suppressive Microglia in Alzheimer's Disease: A New Neuroimmune Regulatory Axis?Cells · 2026Review
- Poly(lactic-co-glycolic acid) immunomodulatory nanoparticles attenuate neuroinflammation and Alzheimer's disease-related pathology in 5xFAD mice.bioRxiv : the preprint server for biology · 2026Article
- IL-10-STAT3-Dependent Transcriptional Regulation in Microglia: Alzheimer's Disease and Neuroinflammation.Biomedicines · 2026Review
- Microglial state transitions are constrained by developmental and metabolic checkpoints.Frontiers in cellular neuroscience · 2026Review
- Cholinergic regulation of neuroinflammation: linking microglia, immunometabolism, and neuromodulation.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
- T cell-microglial interactions that impair myelin maintenance and regeneration: cellular mechanisms on white-matter associated changes.Frontiers in immunology · 2026Review
- From metabolism to neurodegeneration: how microglial functional reprogramming drives neurodegenerative diseases.Frontiers in molecular neuroscience · 2026Review
- TREM2-directed therapy in Alzheimer's disease: from therapeutic window to clinical translation.Frontiers in aging neuroscience · 2026Review
- Early intervention anti-Aβ immunotherapy attenuates microglial activation without inducing exhaustion at residual plaques.Molecular neurodegeneration · 2025Article
- Decoding microglial immunometabolism: a new frontier in Alzheimer's disease research.Molecular neurodegeneration · 2025Review
Corrections and comments
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Authors and funding
41 authors.
Funding
Abstract
Triggering receptor expressed on myeloid cells 2 (TREM2) is a central regulator of microglial activity and loss-of-function coding variants are major risk factors for late onset Alzheimer's disease (LOAD). To better understand the molecular and functional changes associated with TREM2 signalling in microglia, we generated a TREM2 reporter mouse. In APP transgenic animals, bulk RNA-sequencing of isolated microglia sorted based on reporter expression highlighted TREM2 level-related changes in major immunometabolic pathways, and enrichment of genes in oxidative phosphorylation and cholesterol metabolism in microglia with increased TREM2 expression. Metabolic and lipidomic profiling of sorted microglia showed that, independent of Aβ pathology, TREM2 expression correlated with signatures consistent with increased cellular redox, energetics, and cholesterol homoeostasis. In accordance, metabolic activity correlated with phagocytic capacity. Finally, we performed chronic treatment with a TREM2 agonist antibody and identified a window of TREM2 expression where microglia are most responsive, thereby informing clinical applications of TREM2 agonists.
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What Socratic holds
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 Socratic graph.