ArticleFEBS open bio2021
Reduced TREM2 activation in microglia of patients with Alzheimer's disease.
Article in FEBS open bio, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 1 of them a synthesis that pooled it.
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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
20 citing papers in PubMed, 1 synthesis or guideline pooled it, 29 citations in OpenAlex.
- Pooled it
- Microglial dynamics and ferroptosis induction in human iPSC-derived neuron-astrocyte-microglia tri-cultures.FEBS open bio · 2026Article
- Modulating Th17/Treg Balance in Alzheimer's Disease: Therapeutic Insights from Natural Compounds and Immunometabolism.Brain sciences · 2026Review
- Plasma Autoantibodies Against Neurodegeneration-Related Antigens in Dementia and Elevated Chi3Li Autoantibodies in Mild Cognitive Impairment.Biomolecules · 2026Article
- Cholecalciferol (vitamin D3) is an agonist of the Alzheimer's disease-associated immune receptor TREM2.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026Article
- Targeting Microglial Phagocytosis for Alzheimer's Disease Management: Natural, Pharmacological, Nanoparticle, and Gene Therapy Approaches.CNS & neurological disorders drug targets · 2026Review
- Microglial clearance, neuroprotection and cognitive recovery via a novel synthetic sulfolipid in Alzheimer's disease.Journal of neuroinflammation · 2025Article
- Roles of TREM2 in Alzheimer's disease.Translational neurodegeneration · 2025Review
- Amyloid-Related Imaging Abnormality (ARIA) Beyond the APOE-ε4 Allele.Chronic diseases and translational medicine · 2025Review
- Systemic inflammation as a central player in the initiation and development of Alzheimer's disease.Immunity & ageing : I & A · 2025Review
- GAL-201 as a Promising Amyloid-β-Targeting Small-Molecule Approach for Alzheimer's Disease Treatment: Consistent Effects on Synaptic Plasticity, Behavior and Neuroinflammation.International journal of molecular sciences · 2025Article
- Neuraminidase 1 regulates neuropathogenesis by governing the cellular state of microglia via modulation of Trem2 sialylation.Cell reports · 2025Article
- Microglia Gravitate toward Amyloid Plaques Surrounded by Externalized Phosphatidylserine via TREM2.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Microglia play an important role in PRV infection-induced immune responses of the central nervous system.Virology journal · 2023Article
- Article
- Targeting CaN/NFAT in Alzheimer's brain degeneration.Frontiers in immunology · 2023Review
- Novel Anti-Neuroinflammatory Properties of a Thiosemicarbazone-Pyridylhydrazone Copper(II) Complex.International journal of molecular sciences · 2022Article
- Single-Cell Sequencing Analysis of the db/db Mouse Hippocampus Reveals Cell-Type-Specific Insights Into the Pathobiology of Diabetes-Associated Cognitive Dysfunction.Frontiers in endocrinology · 2022Article
- The relationships between neuroglial and neuronal changes in Alzheimer's disease, and the related controversies II:Journal of central nervous system disease · 2022Review
- The Role of Microglia in Alzheimer's Disease From the Perspective of Immune Inflammation and Iron Metabolism.Frontiers in aging neuroscience · 2022Review
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Loss-of-function variants of triggering receptor expressed on myeloid cells 2 (TREM2) increase the risk of developing Alzheimer's disease (AD). The mechanism through which TREM2 contributes to the disease (TREM2 activation vs inactivation) is largely unknown. Here, we analyzed changes in a gene set downstream of TREM2 to determine whether TREM2 signaling is modified by AD progression. We generated an anti-human TREM2 agonistic antibody and defined TREM2 activation in terms of the downstream expression changes induced by this antibody in microglia developed from human induced pluripotent stem cells (iPSC). Differentially expressed genes (DEGs) following TREM2 activation were compared with the gene set extracted from microglial single nuclear RNA sequencing data of patients with AD, using gene set enrichment analysis. We isolated an anti-TREM2-specific agonistic antibody, Hyb87, from anti-human TREM2 antibodies generated using binding and agonism assays, which helped us identify 300 upregulated and 251 downregulated DEGs. Pathway enrichment analysis suggested that TREM2 activation may be associated with Th2-related pathways. TREM2 activation was lower in AD microglia than in microglia from healthy subjects or patients with mild cognitive impairment. TREM2 activation also showed a significant negative correlation with disease progression. Pathway enrichment analysis of DEGs controlled by TREM2 activity indicated that TREM2 activation in AD may lead to anti-apoptotic signaling, immune response, and cytoskeletal changes in the microglia. We showed that TREM2 activation decreases with AD progression, in support of a protective role of TREM2 activation in AD. In addition, the agonistic anti-TREM2 antibody can be used to identify TREM2 activation state in AD microglia.
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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.