ArticleThe Journal of experimental medicine2018
Humanized TREM2 mice reveal microglia-intrinsic and -extrinsic effects of R47H polymorphism.
Article in The Journal of experimental medicine, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 177 papers, 3 of them syntheses that pooled it.
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.
The trial behind it
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
177 citing papers in PubMed, 3 syntheses or guidelines pooled it, 323 citations in OpenAlex.
- Neuroinflammatory markers sTREM2 and YKL-40 in association with Alzheimer's disease pathology: a systematic review and meta-analysis.Molecular psychiatry · 2026Pooled it
- Association of soluble TREM2 with Alzheimer's disease and mild cognitive impairment: a systematic review and meta-analysis.Frontiers in aging neuroscience · 2024Pooled it
- Microglial Phagocytosis: A Disease-Associated Process Emerging from Alzheimer's Disease Genetics.Trends in neurosciences · 2020Pooled it
- The TREM2 agonistic antibody AL002 in early Alzheimer's disease: a phase 2 randomized trial.Nature medicine · 2026Trial
- Preclinical and first-in-human evaluation of AL002, a novel TREM2 agonistic antibody for Alzheimer's disease.Alzheimer's research & therapy · 2024Trial
- Uncovering the biological mechanisms of TREM2 with molecular simulations: A comprehensive review and perspective.Progress in biophysics and molecular biology · 2026Review
- Plasticity of human microglia and brain perivascular macrophages in aging and Alzheimer's disease.Nature genetics · 2026Article
- Chronic pain in Alzheimer disease and the role of neuroimmune interactions.Pharmacological reviews · 2026Review
- The role of Annexin A2 in Alzheimer's disease: From cellular functions to therapeutic potential.The FEBS journal · 2026Review
- Targeting Mitochondrial Dysfunction in Microglia: A New Frontier for Treating Neurodegenerative Diseases.Molecular neurobiology · 2026Review
- Microglial mitophagy as an immunometabolic checkpoint in alzheimer's disease: linking mitochondrial quality control to neuroinflammation.Journal of neuroinflammation · 2026Review
- Mechanisms of increased Alzheimer's disease pathology with R47H and R62H TREM2 variants.Acta neuropathologica · 2026Article
- CD33 Isoform Splicing Dysregulation: A Molecular Determinant of Microglial Dysfunction in Alzheimer's Disease Pathology.Molecular neurobiology · 2026Review
- Decoding TREM2 Signaling Pathways: Linking Macrophage Glycolysis to Inflammatory Diseases in the CNS.Neurology(R) neuroimmunology & neuroinflammation · 2026Review
- Ethanol induces neuroimmune dysregulation and soluble TREM2 generation in a human iPSC neuron, astrocyte, microglia triculture model.Alcohol (Fayetteville, N.Y.) · 2026Article
- Obesity-induced pyroptotic adipocyte death leads to TREM2-dependent macrophage dysfunction and adipose tissue inflammation.iScience · 2026Article
- Interplay between CD33 and TREM2 in Alzheimer's Disease: Potential Mechanistic Insights into Microglial Function in Amyloid Pathology.ACS chemical neuroscience · 2026Review
- The gain-of-function TREM2-T96K mutation increases risk for Alzheimer's disease by impairing microglial function.Neuron · 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
- Microglial phagocytosis in Alzheimer disease.Nature reviews. Neurology · 2026Review
117 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
Alzheimer's disease (AD) is a neurodegenerative disease that causes late-onset dementia. The R47H variant of the microglial receptor TREM2 triples AD risk in genome-wide association studies. In mouse AD models, TREM2-deficient microglia fail to proliferate and cluster around the amyloid-β plaques characteristic of AD. In vitro, the common variant (CV) of TREM2 binds anionic lipids, whereas R47H mutation impairs binding. However, in vivo, the identity of TREM2 ligands and effect of the R47H variant remain unknown. We generated transgenic mice expressing human CV or R47H TREM2 and lacking endogenous TREM2 in the 5XFAD AD model. Only the CV transgene restored amyloid-β-induced microgliosis and microglial activation, indicating that R47H impairs TREM2 function in vivo. Remarkably, soluble TREM2 was found on neurons and plaques in CV- but not R47H-expressing 5XFAD brains, although in vitro CV and R47H were shed similarly via Adam17 proteolytic activity. These results demonstrate that TREM2 interacts with neurons and plaques duing amyloid-β accumulation and R47H impairs this interaction.
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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.