ArticleCell2015
TREM2 lipid sensing sustains the microglial response in an Alzheimer's disease model.
Article in Cell, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1,101 papers, 2 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
1,101 citing papers in PubMed, 2 syntheses or guidelines pooled it, 1,743 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
- GWAS meta-analysis of cerebrospinal fluid Alzheimer's biomarkers reveals loci regulating lipids, brain volume and autophagy.Nature communications · 2026Pooled it
- The TREM2 agonistic antibody AL002 in early Alzheimer's disease: a phase 2 randomized trial.Nature medicine · 2026Trial
- Trial
- An aging-sensitive secreted phospholipase confers neuroprotection and cognitive resilience.Nature neuroscience · 2026Article
- Article
- Dynamic metabolic programming of monocyte-derived cells defines immunity in CNS disease.Brain : a journal of neurology · 2026Review
- Apoptotic cell overload drives multinucleated giant cell formation after neoadjuvant chemotherapy in colorectal cancer: molecular mechanisms and tumor-suppressive effects.Cell death & disease · 2026Article
- Lipidome alteration as a hallmark and therapeutic target in Alzheimer's disease.Neural regeneration research · 2026Article
- Small-molecule TREM2 agonists: From artificial intelligence driven discovery to therapeutic application in Alzheimer's disease.Neural regeneration research · 2026Article
- DHA deficiency drives neural oxidized-lipid stress and microglial activation.bioRxiv : the preprint server for biology · 2026Article
- TREM2 Attenuates Microglial Pyroptosis in Sepsis-Associated Encephalopathy Through Modulation of the mtDNA-cGAS-STING Pathway.Molecular neurobiology · 2026Article
- 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
- The TREM2 R47H variant is associated with liver-plasma-brain axis dyshomeostasis in the 5xFAD mouse model of Alzheimer's disease.Neurobiology of aging · 2026Article
- Alzheimer's disease through the lens of mesenchymal drift: the collapse of cellular identity.BMB reports · 2026Review
- Identification of a spatially organized TREM2-associated permissive macrophage niche in human pulmonary tuberculosis alveolar pneumonia.Nature communications · 2026Article
- CD36-mediated lipid-accumulation in reactive microglia contributes to retinal degeneration via the NLRP3-IL-1β pathway in mice.Nature communications · 2026Article
- Theranostic Innovative Strategies for Brain Diseases: New Insights on Neurovascular Unit-Associated Pathological Changes in Neurodegenerative Disorders and Aging.International journal of molecular sciences · 2026Review
- LINC00926 promotes microglial M1 polarization and neuroinflammation by sponging miR-383-3p in Alzheimer's disease: a potential diagnostic and therapeutic target.Acta neurologica Belgica · 2026Article
1,041 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
Authors and funding
13 authors at 2 institutions in 1 country.
Funding
Abstract
Triggering receptor expressed on myeloid cells 2 (TREM2) is a microglial surface receptor that triggers intracellular protein tyrosine phosphorylation. Recent genome-wide association studies have shown that a rare R47H mutation of TREM2 correlates with a substantial increase in the risk of developing Alzheimer's disease (AD). To address the basis for this genetic association, we studied TREM2 deficiency in the 5XFAD mouse model of AD. We found that TREM2 deficiency and haploinsufficiency augment β-amyloid (Aβ) accumulation due to a dysfunctional response of microglia, which fail to cluster around Aβ plaques and become apoptotic. We further demonstrate that TREM2 senses a broad array of anionic and zwitterionic lipids known to associate with fibrillar Aβ in lipid membranes and to be exposed on the surface of damaged neurons. Remarkably, the R47H mutation impairs TREM2 detection of lipid ligands. Thus, TREM2 detects damage-associated lipid patterns associated with neurodegeneration, sustaining the microglial response to Aβ accumulation.
Indexed as
Identifiers
What OpenQuestion 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 OpenQuestion graph.