ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2024
Neutral or Detrimental Effects of TREM2 Agonist Antibodies in Preclinical Models of Alzheimer's Disease and Multiple Sclerosis.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers, 1 of them a synthesis that pooled it.
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Who cites it
25 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Gain-of-function Modulation of TREM2 and its Impact on Amyloid-β and Tau Pathologies in Alzheimer's Disease: A Systematic Review and Meta-analysis of Animal Studies.Molecular neurobiology · 2026Pooled it
- TREM2 in neurodegenerative diseases and acute neurological injuries: mechanisms to targeted therapies.Cell communication and signaling : CCS · 2026Review
- Axonopathy: mechanisms and potential therapeutic targets for neurodegenerative diseases.Translational neurodegeneration · 2026Review
- Phagocytosis and neuroinflammation: orchestrating central nervous system homeostasis, repair, and the resolution of inflammation.Trends in neurosciences · 2026Review
- Immune dysfunction in Alzheimer disease.Nature reviews. Neuroscience · 2026Review
- 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
- Nutritional substrates and microglial metabolic fitness in brain aging and Alzheimer's disease: from lipid handling to TREM2-linked translation.Frontiers in nutrition · 2026Review
- TREM2 and microglial immunity in Alzheimer's disease: mechanisms, genetics, and therapeutic opportunities.Frontiers in immunology · 2026Review
- Targeting microglia-mediated neuroinflammation in Alzheimer's disease: mechanisms and therapeutic approaches.Frontiers in immunology · 2026Review
- Revisiting TREM2: from multi-omics signaling networks to clinical translation.Frontiers in immunology · 2026Review
- Article
- Roles of TREM2 in Alzheimer's disease.Translational neurodegeneration · 2025Review
- Pathological mechanisms and treatment progression of Alzheimer's disease.European journal of medical research · 2025Review
- TREM2-mediated regulation of microglial activity: a promising target for the treatment of ischemic stroke.Journal of translational medicine · 2025Review
- Identification of conserved and tissue-restricted transcriptional profiles for lipid associated macrophages.Communications biology · 2025Article
- Acute TREM2 inhibition depletes MAFB-high microglia and hinders remyelination.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- CD33 Ameliorates Surgery-Induced Spatial Learning and Memory Impairments Through TREM2.Molecular neurobiology · 2025Article
- Beyond Amyloid and Tau: The Critical Role of Microglia in Alzheimer's Disease Therapeutics.Biomedicines · 2025Review
- Unraveling the inflammation-degeneration tangle in early MS: preliminary insights from ferritin, neurogranin, TREM2, and retinal ganglion cell layer.Journal of neurology · 2025Article
- TREM2 signaling pathway in sepsis-induced acute lung injury: physiology, pathology, and therapeutic applications.Frontiers in medicine · 2025Review
Corrections and comments
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Authors and funding
42 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Human genetics and preclinical studies have identified key contributions of TREM2 to several neurodegenerative conditions, inspiring efforts to modulate TREM2 therapeutically. Here, we characterize the activities of three TREM2 agonist antibodies in multiple mixed-sex mouse models of Alzheimer's disease (AD) pathology and remyelination. Receptor activation and downstream signaling are explored in vitro, and active dose ranges are determined in vivo based on pharmacodynamic responses from microglia. For mice bearing amyloid-β (Aβ) pathology (PS2APP) or combined Aβ and tau pathology (TauPS2APP), chronic TREM2 agonist antibody treatment had limited impact on microglia engagement with pathology, overall pathology burden, or downstream neuronal damage. For mice with demyelinating injuries triggered acutely with lysolecithin, TREM2 agonist antibodies unexpectedly disrupted injury resolution. Likewise, TREM2 agonist antibodies limited myelin recovery for mice experiencing chronic demyelination from cuprizone. We highlight the contributions of dose timing and frequency across models. These results introduce important considerations for future TREM2-targeting approaches.
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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.