ArticleAlzheimer's & dementia : the journal of the Alzheimer's Association2020
Functional insights from biophysical study of TREM2 interactions with apoE and Aβ
Article in Alzheimer's & dementia : the journal of the Alzheimer's Association, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.
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Who cites it
55 citing papers in PubMed, 68 citations in OpenAlex.
- Uncovering the biological mechanisms of TREM2 with molecular simulations: A comprehensive review and perspective.Progress in biophysics and molecular biology · 2026Review
- APOEε4 attenuates early TREM2-mediated microglial responses and influences disease trajectories in dementia with Lewy bodies.Research square · 2026Article
- Reshaping the immune landscape: next-generation microglia-targeted therapies for Alzheimer's disease.Biological research · 2026Review
- TREM2 drives monocyte-derived macrophage responses tobioRxiv : the preprint server for biology · 2026Article
- XL-MS and De Novo Protein Design Identified a Common Motif for TREM2 Binding.bioRxiv : the preprint server for biology · 2026Article
- Dual Role of Microglial TREM2 in Neuronal Degeneration and Regeneration After Axotomy.bioRxiv : the preprint server for biology · 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
- Decoding TREM2 Signaling Pathways: Linking Macrophage Glycolysis to Inflammatory Diseases in the CNS.Neurology(R) neuroimmunology & neuroinflammation · 2026Review
- TREM2 activation by first-in-class direct small molecule agonists: DEL screening, optimization, biophysical validation, and functional characterization.European journal of medicinal chemistry · 2026Article
- Alterations in the brain lipidome of Alzheimer's disease donors with rareBrain communications · 2026Article
- TREM2-directed therapy in Alzheimer's disease: from therapeutic window to clinical translation.Frontiers in aging neuroscience · 2026Review
- Roles of TREM2 in Alzheimer's disease.Translational neurodegeneration · 2025Review
- Lipid and lipoprotein metabolism in microglia: Alzheimer's disease mechanisms and interventions.Journal of lipid research · 2025Review
- TREM2-apoE3 interactions and Alzheimer's disease: Molecular and structural insights and effects of TREM2 R47H and apoE4 variants.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Is TREM2 a Stretch: Implications of TREM2 Along Spinal Cord Circuits in Health, Aging, Injury, and Disease.Cells · 2025Review
- The flexible stalk domain of sTREM2 modulates its interactions with brain-based phospholipids.eLife · 2025Article
- Review
- TREM2 hit discovery using temperature-related intensity change (TRIC) technology: A proof-of-concept high-throughput screening approach.SLAS discovery : advancing life sciences R & D · 2025Article
- ARNature communications · 2025Article
- Cerebrospinal fluid sTREM2 mediates the associations of α-synuclein with tau pathology in older adults without dementia: two population-based study.Journal of translational medicine · 2025Article
Corrections and comments
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Authors and funding
14 authors at 4 institutions in 1 country.
Funding
Abstract
introductionTriggering receptor expressed on myeloid cells-2 (TREM2) is an immune receptor expressed on microglia that also can become soluble (sTREM2). How TREM2 engages different ligands remains poorly understood.
methodsWe used comprehensive biolayer interferometry (BLI) analysis to investigate TREM2 and sTREM2 interactions with apolipoprotein E (apoE) and monomeric amyloid beta (Aβ) (mAβ42).
resultsTREM2 engagement of apoE was protein mediated with little effect of lipidation, showing slight affinity differences between isoforms (E4 > E3 > E2). Another family member, TREML2, did not bind apoE. Disease-linked TREM2 variants within a "basic patch" minimally impact apoE binding. Instead, TREM2 uses a unique hydrophobic surface to bind apoE, which requires the apoE hinge region. TREM2 and sTREM2 directly bind mAβ42 and potently inhibit Aβ42 polymerization, suggesting a potential role for soluble sTREM2 in preventing AD pathogenesis. DISCUSSION: These findings demonstrate that TREM2 has at least two ligand-binding surfaces that might be therapeutic targets and uncovers a potential function for sTREM2 in directly inhibiting Aβ polymerization.
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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.