ArticleCell2017
TREM2 Maintains Microglial Metabolic Fitness in Alzheimer's Disease.
Article in Cell, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 797 papers, 2 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
797 citing papers in PubMed, 2 syntheses or guidelines pooled it, 1,205 citations in OpenAlex.
- The role of AI-assisted drug repurposing in neurological disorders: a systematic review of validation strategies, challenges and opportunities.Journal of nanobiotechnology · 2026Pooled it
- Pooled it
- Short-chain fatty acid-producing commensals: Key modulators of AD neuroinflammation via the microbiota-gut-brain axis.Current research in microbial sciences · 2026Review
- Failure of Neuroinflammatory Resolution in Brain Aging: Molecular Mechanisms and an Integrative Framework of Microglial Inflammometabolic Locking.Molecular neurobiology · 2026Review
- Exercise promotes lipophagy and mitigates cognitive impairment in Alzheimer's disease through downregulating microglial TMEM9.Translational neurodegeneration · 2026Article
- MD2-IN-1 restores microglial lysosomal function and attenuates amyloid pathology through TREM2-associated signaling in 5×FAD mice.Acta pharmacologica Sinica · 2026Article
- Context-dependent TREM2 signalling in myeloid cells: Molecular mechanisms and immunotherapeutic divergence in neurodegeneration and cancer.Clinical and translational medicine · 2026Review
- Cell-based immunotherapy for neurodegenerative disease: A promising avenue.Neural regeneration research · 2026Article
- Spatiotemporal heterogeneity and dynamic evolution of microglial glucose metabolic reprogramming in Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Review
- Chronic Radiation-Induced Wounds: Pathogenesis, Current Therapeutic Strategies, and Emerging Regenerative Approaches.International journal of molecular sciences · 2026Review
- Review
- Genetic Prioritization of Plasma Proteins Across Dementia Subtypes: A Proteome-Wide Mendelian Randomization and Bayesian Colocalization Analysis.Cellular and 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
- Aberrant phase separation from a rare ABI3 mutation drives microglial dysfunction and Alzheimer's risk.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- A Rosella-PLIN2 knock-in mouse reveals lipophagy and immunometabolic interplay in atherosclerosis.Autophagy · 2026Article
- Roles of autophagy in brain homeostasis and disease.Nature neuroscience · 2026Review
- Reduced microvascular coverage links a hypoxia-associated niche to microglial autophagic dysfunction in Parkinson's disease.Acta neuropathologica communications · 2026Article
- Article
- TREM2 mediates macrophage suppression of NLRP3 inflammasome pathway to promote non-small cell lung cancer progression.Molecular and cellular biochemistry · 2026Article
737 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
19 authors at 3 institutions in 2 countries.
Funding
Abstract
Elevated risk of developing Alzheimer's disease (AD) is associated with hypomorphic variants of TREM2, a surface receptor required for microglial responses to neurodegeneration, including proliferation, survival, clustering, and phagocytosis. How TREM2 promotes such diverse responses is unknown. Here, we find that microglia in AD patients carrying TREM2 risk variants and TREM2-deficient mice with AD-like pathology have abundant autophagic vesicles, as do TREM2-deficient macrophages under growth-factor limitation or endoplasmic reticulum (ER) stress. Combined metabolomics and RNA sequencing (RNA-seq) linked this anomalous autophagy to defective mammalian target of rapamycin (mTOR) signaling, which affects ATP levels and biosynthetic pathways. Metabolic derailment and autophagy were offset in vitro through Dectin-1, a receptor that elicits TREM2-like intracellular signals, and cyclocreatine, a creatine analog that can supply ATP. Dietary cyclocreatine tempered autophagy, restored microglial clustering around plaques, and decreased plaque-adjacent neuronal dystrophy in TREM2-deficient mice with amyloid-β pathology. Thus, TREM2 enables microglial responses during AD by sustaining cellular energetic and biosynthetic metabolism.
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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.