ArticleScientific reports2017
TREM2 promotes Aβ phagocytosis by upregulating C/EBPα-dependent CD36 expression in microglia.
Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 86 papers, 1 of them a synthesis that pooled it.
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Who cites it
86 citing papers in PubMed, 1 synthesis or guideline pooled it, 157 citations in OpenAlex.
- Identification of methylation-regulated genes modulating microglial phagocytosis in hyperhomocysteinemia-exacerbated Alzheimer's disease.Alzheimer's research & therapy · 2023Pooled it
- Distinct single-nucleus RNA-seq changes among non-neuronal cells in ADNC, LATE-NC, and mixed pathologies.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Cholesterol at the Center of Alzheimer's Disease: A Unifying Hypothesis on the Pathogenic Mechanism.Molecules (Basel, Switzerland) · 2026Review
- TREM2 Regulates Microglial Activation via the ERK/p38 Signaling Pathway: Implications for the Pathogenesis of Experimental Autoimmune Uveitis.Investigative ophthalmology & visual science · 2026Article
- NLRP6 governs hippocampal microglial phagocytosis to resist stress-induced depressive-like behaviors in mice and the intervention effect of bezafibrate.Journal of advanced research · 2026Article
- The Effect of Metabolic Syndrome on Alzheimer's Disease: Physical Activity as a Preventive and Therapeutic Measure.Brain sciences · 2026Review
- Dual Targeting of Tau Kinases and Autophagy by Abemaciclib Independent of CDK4/6 Inhibition.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- A ligand-mimetic anti-TREM2 agonist antibody elevates soluble TREM2 and ameliorates pathology in mouse models of Alzheimer's disease and multiple sclerosis.Journal of neuroinflammation · 2026Article
- Interplay between Peripheral and Central Nervous System Myeloid Cells during Aging: Impact for Lade-Life Depression and Alzheimer's Disease.Neuroimmunomodulation · 2026Review
- TREM2-directed therapy in Alzheimer's disease: from therapeutic window to clinical translation.Frontiers in aging neuroscience · 2026Review
- Microglial clearance, neuroprotection and cognitive recovery via a novel synthetic sulfolipid in Alzheimer's disease.Journal of neuroinflammation · 2025Article
- Targeting Microglial Activation to Modulate Neuroinflammation in Alzheimer's Disease.Neuromolecular medicine · 2025Review
- Roles of TREM2 in Alzheimer's disease.Translational neurodegeneration · 2025Review
- Potential Risk to Brain Health after Surgical Interventions: Biomarkers to Predict the Occurrence of Cognitive Decline.Aging and disease · 2025Review
- Mapping Macrophage Diversity in Coats' Disease: A Lipid-Associated Subset in the Pathogenesis of Exudative Retinopathy.Investigative ophthalmology & visual science · 2025Article
- Microglial Dysfunction and Amyloid-Beta Pathology in Alzheimer's Disease and HIV-Associated Neurocognitive Disorders.International journal of molecular sciences · 2025Review
- Unraveling the complex role of microglia in Alzheimer's disease: amyloid β metabolism and plaque formation.Inflammation and regeneration · 2025Review
- Visualising the Knowledge Structure of Microglia in Alzheimer's Disease: A CiteSpace Analysis.Journal of multidisciplinary healthcare · 2025Article
- Dulaglutide Alleviates Alzheimer's Disease by Regulating Microglial Polarization and Neurogenic Activity.Combinatorial chemistry & high throughput screening · 2025Article
- The various roles of TREM2 in cardiovascular disease.Frontiers in immunology · 2025Review
26 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
14 authors at 6 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
TREM2 plays a critical role in the alleviation of Alzheimer's disease by promoting Aβ phagocytosis by microglia, but the detailed molecular mechanism underlying TREM2-induced direct phagocytic activity of Aβ remains to be revealed. We found that learning and memory functions were improved in aged TREM2 TG mice, with the opposite effects in KO mice. The amount of phagocytosed Aβ was significantly reduced in the primary microglia of KO mice. CD36 expression in primary microglia was greater in TG than in WT mice but was substantially decreased in KO mice. The expression of C/EBPα, an upstream transcriptional activator of CD36, was also elevated in primary microglia of TG mice but decreased in KO mice. The transcription of CD36 was markedly increased by TREM2 overexpression, and this effect was suppressed by a mutation of the C/EBPα binding site on the CD36 promoter. The TREM2-induced expression of CD36 and C/EBPα was inhibited by treatment with PI3K/AKT signaling blockers, and phosphorylation of AKT was elevated in TREM2-overexpressing BV2 cells. The present study provides evidence that TREM2 is required for preventing loss of memory and learning in Alzheimer's disease by regulating C/EBPα-dependent CD36 expression and the consequent Aβ phagocytosis.
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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.