TREM2
Entity Detail — Knowledge Graph Node
Understanding Entity Pages
This page aggregates everything SciDEX knows about TREM2: its mechanistic relationships (Knowledge Graph edges), hypotheses targeting it, analyses mentioning it, and supporting scientific papers. The interactive graph below shows its immediate neighbors. All content is AI-synthesized from peer-reviewed literature.
Summary
A gene referenced in 1 knowledge graph relationship. Key connections: encodes TREM2_protein (protein).
AI-generated illustration · click image to enlarge
Regenerate portrait ↻| Gene Symbol | TREM2 |
| Full Name | Triggering Receptor Expressed on Myeloid Cells 2 |
| Aliases | TREM-2 |
| Chromosome | 6p21.1 |
| Protein Type | Receptor |
| Target Class | Receptor |
| Function | Lipid sensing; Debris clearance; Microglial activation |
| Mechanism of Action | Agonist antibodies that enhance TREM2 signaling to promote microglial function |
| Primary Expression | Microglia, Cerebral cortex, Hippocampus |
| Druggability | Low (0.42) |
| Clinical Stage | Phase II |
| Molecular Weight | 35 kDa |
| Amino Acids | 231 aa |
| Exons | 5 |
| Pathways | Innate immunity, Phagocytosis, DAP12-SYK signaling |
| UniProt ID | Q9NZC2 |
| NCBI Gene ID | 54209 |
| Ensembl ID | ENSG00000095970 |
| OMIM | 605086 |
| GeneCards | TREM2 |
| Human Protein Atlas | TREM2 |
| Associated Diseases | 1-bromopropane neurotoxicity, AD risk, aging, Als |
| Known Drugs/Compounds | aducanumab, AL002, Al002C, AL002C, amyloid deposits, anti-TREM2 antibodies |
| Interactions | A2M, AB, ABCA1, ABCA7, ABCG1, ABETA |
| SciDEX Target | View Target Profile (1 clinical trials) |
| SciDEX Hypotheses | TREM2-Dependent Astrocyte-Microglia Cross-talk in H1: TREM2 Agonism to Redirect APOE4-Enhanced Micro TREM2-Mediated Astrocyte-Microglia Cross-Talk in N (+89 more) |
| KG Connections | 3566 knowledge graph edges |
| Databases | GeneCardsHPASTRING |
🧬 3D Structure Comparison — TREM2 Experimental (PDB) vs Predicted (AlphaFold) — click to expand
Wiki Pages (21)
Knowledge base pages for this entity
microglial-synaptic-pruning-dysregulation
mechanism · 3254 wordsTREM2 Microglial Signaling Pathway in Neurodegeneration
mechanism · 4613 wordsTREM2→Microglial Dysfunction→Alzheimer's Disease Causal Chain
mechanism · 3665 wordsTREM2 in Frontotemporal Dementia
mechanism · 3364 wordsTREM2 Signaling in Neurodegeneration
mechanism · 3362 wordsTREM2 in Parkinson's Disease — Cross-Disease Therapeutic Opportunity
mechanism · 3181 wordsPathway Diagram
graph TD
TREM2["TREM2 Receptor"] -->|"Recognizes"| Ligands["Lipids, Apolipoproteins"]
TREM2 -->|"Signals via"| DAP12["DAP12 Adapter"]
DAP12 -->|"Activates"| SYK["SYK Kinase"]
SYK -->|"Downstream"| PI3K["PI3K/AKT"]
SYK -->|"Downstream"| MAPK["MAPK Pathway"]
PI3K -->|"Promotes"| Survival["Cell Survival"]
MAPK -->|"Induces"| Phagocytosis["Phagocytosis"]
TREM2 -->|"Modulates"| Inflammation["Inflammatory Response"]
TREM2 -.Loss-of-function.-> AD["Alzheimer's Risk"]Outgoing (1919)
| Target | Relation | Type | Str |
|---|---|---|---|
| benchmark_ot_ad_answer_key:TREM2 | data_in | dataset_row | 0.00 |
| ds-f50762b67605 | provides_data_for | dataset | 1.00 |
| Als | activates | disease | 1.00 |
| ds-db4a006ea647 | provides_data_for | dataset | 1.00 |
| NEUROINFLAMMATION | activates | gene | 1.00 |
| Alzheimer | regulates | disease | 1.00 |
| ds-f2c28aed24a7 | provides_data_for | dataset | 1.00 |
| ALZHEIMER'S DISEASE | therapeutic_target | gene | 1.00 |
| MICROGLIA | regulates | cell_type | 1.00 |
| MICROGLIA | expressed_in | cell_type | 1.00 |
| ds-83b31ef18d49 | provides_data_for | dataset | 1.00 |
| Neuroinflammation | therapeutic_target | disease | 1.00 |
| Alzheimer | associated_with | disease | 1.00 |
| ALZHEIMER | therapeutic_target | gene | 1.00 |
| NEURODEGENERATION | associated_with | disease | 1.00 |
| ALZHEIMER'S DISEASE | activates | gene | 1.00 |
| Neuroinflammation | activates | disease | 1.00 |
| Inflammation | therapeutic_target | disease | 1.00 |
| MICROGLIA | associated_with | gene | 1.00 |
| Alzheimer | activates | disease | 1.00 |
| MICROGLIA | activates | gene | 1.00 |
| ALZHEIMER | activates | gene | 1.00 |
| Inflammation | inhibits | disease | 1.00 |
| GENES | associated_with | gene | 1.00 |
| neurodegeneration | associated_with | disease | 1.00 |
| ALZHEIMER'S DISEASE | associated_with | gene | 1.00 |
| Inflammation | activates | disease | 1.00 |
| Alzheimer | therapeutic_target | disease | 1.00 |
| Neurodegeneration | associated_with | disease | 1.00 |
| ALZHEIMERS | associated_with | disease | 1.00 |
| ds-6784494f1741 | provides_data_for | dataset | 1.00 |
| Alzheimer | expressed_in | disease | 1.00 |
| APOE | activates | protein | 1.00 |
| ALZHEIMER | associated_with | gene | 1.00 |
| ALZHEIMER | regulates | gene | 1.00 |
| Phagocytosis | activates | pathway | 1.00 |
| ALZHEIMER | expressed_in | gene | 1.00 |
| ALZHEIMER'S DISEASE | regulates | gene | 1.00 |
| AMYLOID | inhibits | gene | 1.00 |
| Immune Response | activates | pathway | 1.00 |
| PHAGOCYTOSIS | activates | gene | 1.00 |
| NEUROINFLAMMATION | therapeutic_target | gene | 1.00 |
| ALZHEIMER'S DISEASE | expressed_in | gene | 1.00 |
| TREM2_R47H | is_variant_of | variant | 0.97 |
| DAM | drives | cell_type | 0.96 |
| GBM progression | prevents | process | 0.95 |
| PARKINSON'S DISEASE | protects_against | disease | 0.95 |
| Strem2 | expressed_in | protein | 0.95 |
| Als | associated_with | disease | 0.95 |
| immunosuppression | regulates | process | 0.95 |
Incoming (1655)
| Source | Relation | Type | Str |
|---|---|---|---|
| entities-microglia-in-neurodegeneration | associated_with | wiki | 0.00 |
| ad_genetic_risk_loci:TREM2 | data_in | dataset_row | 0.00 |
| benchmark_ot_ad_answer_key:TREM2 | data_in | dataset_row | 0.00 |
| entities-microglia-in-neurodegeneration | interacts_with | wiki | 0.00 |
| h-immunity-c3bc272f | relates_to | hypothesis | 0.00 |
| h-immunity-c64967ab | relates_to | hypothesis | 0.00 |
| MICROGLIA | associated_with | gene | 1.00 |
| ds-db4a006ea647 | data_in | dataset | 1.00 |
| AMYLOID | associated_with | protein | 1.00 |
| ds-f2c28aed24a7 | data_in | dataset | 1.00 |
| ds-f50762b67605 | data_in | dataset | 1.00 |
| ds-83b31ef18d49 | data_in | dataset | 1.00 |
| ds-6784494f1741 | data_in | dataset | 1.00 |
| MICROGLIA | expressed_in | cell_type | 1.00 |
| MICROGLIA | activates | gene | 1.00 |
| APOE | associated_with | gene | 1.00 |
| NEURODEGENERATION | associated_with | gene | 1.00 |
| ALZHEIMER'S DISEASE | associated_with | gene | 1.00 |
| TAU | associated_with | gene | 0.98 |
| PARKINSON'S DISEASE | associated_with | disease | 0.98 |
| MICROGLIA | inhibits | gene | 0.98 |
| h-61196ade | targets | hypothesis | 0.95 |
| Microglia | expressed_in | cell_type | 0.95 |
| DAM | requires | cell_type | 0.94 |
| APOE | binds_to | gene | 0.92 |
| AL002C | activates | drug | 0.90 |
| MICROGLIA | regulates | gene | 0.90 |
| galectin-3 | binds_to | protein | 0.90 |
| ALZHEIMER DISEASE | associated_with | gene | 0.90 |
| Mutant THAP11 | upregulates | protein | 0.90 |
| ADAM Proteases | mediates | enzyme | 0.90 |
| NLRP3 | associated_with | gene | 0.90 |
| Al002C | activates | drug | 0.90 |
| anti-TREM2 antibodies | activates | drug | 0.90 |
| h-trem2-6a46fa2c | targets_gene | hypothesis | 0.90 |
| Rmab38E2-Scfv8D3 | upregulates | drug | 0.90 |
| SDA-2026-04-02-gap-tau-prop-20260402003221-H002 | targets | hypothesis | 0.90 |
| h-trem2-f3effd21 | targets_gene | hypothesis | 0.90 |
| h-5afacdfe | targets_gene | hypothesis | 0.90 |
| ALZHEIMER'S DISEASE | expressed_in | gene | 0.90 |
| h-e003a35e | targets | hypothesis | 0.90 |
| h-var-ddd5c9bcc8 | targets_gene | hypothesis | 0.90 |
| h-trem2-8df94363 | targets_gene | hypothesis | 0.90 |
| GAL3 | interacts_with | protein | 0.90 |
| h-var-bed9f3b7ed | targets_gene | hypothesis | 0.90 |
| h-7f2d0e21 | targets_gene | hypothesis | 0.90 |
| h-044ee057 | targets | hypothesis | 0.90 |
| h-trem2-fe8c644a | targets_gene | hypothesis | 0.90 |
| h-var-ce41f0efd7 | targets_gene | hypothesis | 0.90 |
| h-ea3274ff | targets | hypothesis | 0.90 |
Targeting Hypotheses (30)
Hypotheses where this entity is a therapeutic target
Mentioning Analyses (30)
Scientific analyses that reference this entity
TREM2 in Alzheimer's Disease: Mechanisms, Therapeutics, and Biomarkers
neurodegeneration | 2026-04-26 | 8 hypotheses Top: 0.990
What are the mechanisms by which microglial senescence contributes to ALS pathol
neurodegeneration | 2026-04-26 | 10 hypotheses Top: 0.799
Does the cancer-cystatin-C-TREM2 pathway protect against tau pathology and other
neurodegeneration | 2026-04-25 | 8 hypotheses Top: 0.640
Does Alectinib truly bind C1q directly with high affinity, or is this an experim
molecular biology | 2026-04-21 | 1 hypotheses Top: 0.582
Microglial subtypes in neurodegeneration — friend vs foe
neurodegeneration | 2026-04-17 | 7 hypotheses Top: 0.685
Experiments (20)
Experimental studies targeting or related to this entity
| Experiment | Type | Disease | Score | Feasibility | Model | Status | Est. Cost |
|---|---|---|---|---|---|---|---|
| NAD depletion effects on monocyte/macrophage differentiation | exploratory | Inflammatory bowel disease | 0.900 | 0.00 | Primary mouse and human monocy | proposed | N/A |
| FK866 treatment in DSS-induced colitis mouse model | validation | Inflammatory bowel disease (co | 0.900 | 0.00 | DSS-induced colitis mice | proposed | N/A |
| FK866 in azoxymethane/DSS colitis-associated cancer model | validation | Colitis-associated cancer | 0.850 | 0.00 | AOM/DSS-treated mice | proposed | N/A |
| FK866 mechanism validation in Rag1-/- mice | validation | Inflammatory bowel disease | 0.850 | 0.00 | Rag1-/- mice with DSS-induced | proposed | N/A |
| TREM2 KO amyloid pathology study | validation | Alzheimers Disease | 0.800 | 0.00 | Mouse (5xFAD/TREM2-/-) | completed | N/A |
| TREM2 KO amyloid pathology study | validation | Alzheimers Disease | 0.800 | 0.00 | Mouse (5xFAD/TREM2-/-) | completed | N/A |
| TREM2 KO amyloid pathology study | validation | Alzheimers Disease | 0.800 | 0.00 | Mouse (5xFAD/TREM2-/-) | completed | N/A |
| TREM2 KO amyloid pathology study | validation | Alzheimers Disease | 0.800 | 0.00 | Mouse (5xFAD/TREM2-/-) | completed | N/A |
| TREM2 KO amyloid pathology study | validation | Alzheimers Disease | 0.800 | 0.00 | Mouse (5xFAD/TREM2-/-) | completed | N/A |
| TREM2 KO amyloid pathology study | validation | Alzheimers Disease | 0.800 | 0.00 | Mouse (5xFAD/TREM2-/-) | in_progress | N/A |
| TREM2 KO amyloid pathology study | validation | Alzheimers Disease | 0.800 | 0.00 | Mouse (5xFAD/TREM2-/-) | completed | N/A |
| TREM2 KO amyloid pathology study | validation | Alzheimers Disease | 0.800 | 0.00 | Mouse (5xFAD/TREM2-/-) | completed | N/A |
| TREM2 KO amyloid pathology study | validation | Alzheimers Disease | 0.800 | 0.00 | Mouse (5xFAD/TREM2-/-) | completed | N/A |
| TREM2 KO amyloid pathology study | validation | Alzheimers Disease | 0.800 | 0.00 | Mouse (5xFAD/TREM2-/-) | completed | N/A |
| TREM2 KO amyloid pathology study | validation | Alzheimers Disease | 0.800 | 0.00 | Mouse (5xFAD/TREM2-/-) | completed | N/A |
| TREM2 KO amyloid pathology study | validation | Alzheimers Disease | 0.800 | 0.00 | Mouse (5xFAD/TREM2-/-) | completed | N/A |
| TREM2 KO amyloid pathology study | validation | Alzheimers Disease | 0.800 | 0.00 | Mouse (5xFAD/TREM2-/-) | completed | N/A |
| TREM2 KO amyloid pathology study | validation | Alzheimers Disease | 0.800 | 0.00 | Mouse (5xFAD/TREM2-/-) | completed | N/A |
| TREM2 KO amyloid pathology study | validation | Alzheimers Disease | 0.800 | 0.00 | Mouse (5xFAD/TREM2-/-) | completed | N/A |
| TREM2 Agonist Antibody Rescue of Astrocyte-Microglia Signalling in 5xF | in_vivo | Alzheimer's disease | 0.794 | 0.72 | 5xFAD transgenic mice (n=15/gr | proposed | $85,000 |
Related Papers (15)
Scientific publications cited in analyses involving this entity
| Title & PMID | Authors | Journal | Year | Citations |
|---|---|---|---|---|
| Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and TREM2- [PMID:31932797] | Zhou Y, Song WM, Andhey PS, Swain A, Lev | Nat Med | 2020 | 1 |
| Enhancing TREM2 expression activates microglia and modestly mitigates tau pathol [PMID:40122810] | ["Chen Kai", "Li Fuyao", "Zhang Shuwen", | Journal of neuroinflammation | 2025 | 0 |
| The cholesterol 24-hydroxylase CYP46A1 promotes α-synuclein pathology in Parkins [PMID:39964974] | Dai L, Wang J, Meng L, Zhang X, Xiao T, | PLoS biology | 2025 | 0 |
| Emerging Molecular Targets in Neurodegenerative Disorders: New Avenues for Thera [PMID:40922457] | ["Eroglu E", "Harmanci N"] | Basic & clinical pharmacology | 2025 | 0 |
| Microglia, Trem2, and Neurodegeneration. [PMID:38769824] | Shi Q, Gutierrez RA, Bhat MA | Neuroscientist | 2025 | 0 |
| Microglia, Trem2, and Neurodegeneration. [PMID:38769824] | Shi Q, Gutierrez RA, Bhat MA | The Neuroscientist : a review | 2025 | 0 |
| Enhancing TREM2 expression activates microglia and modestly mitigates tau pathol [PMID:40122810] | ["Chen Kai", "Li Fuyao", "Zhang Shuwen", | Journal of neuroinflammation | 2025 | 0 |
| The role of microglial TREM2 in development: A path toward neurodegeneration? [PMID:38837837] | ["Matteoli Michela"] | Glia | 2024 | 0 |
| TREM2 receptor protects against complement-mediated synaptic loss by binding to [PMID:37442133] | Zhong L, Sheng X, Wang W, Li Y, Zhuo R, | Immunity | 2023 | 0 |
| Oxidized phosphatidylcholines found in multiple sclerosis lesions mediate neurod [PMID:33603230] | Dong Y, D'Mello C, Pinsky W, Lozinski BM | Nature neuroscience | 2021 | 0 |
| Neurodegeneration and Inflammation-An Interesting Interplay in Parkinson's Disea [PMID:33182554] | Marogianni C, Sokratous M, Dardiotis E, | International journal of molec | 2020 | 0 |
| Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and TREM2- [PMID:31932797] | Zhou Y, Song WM, Andhey PS, Swain A, Lev | Nat Med | 2020 | 0 |
| Neurodegeneration and Inflammation-An Interesting Interplay in Parkinson's Disea [PMID:33182554] | Marogianni C, Sokratous M, Dardiotis E, | International journal of molec | 2020 | 0 |
| Multiple Sclerosis Pathology. [PMID:29358320] | Lassmann H | Cold Spring Harbor perspective | 2018 | 0 |
| Recent Advances from the Bench Toward the Bedside in Alzheimer's Disease [PMID:26137544] | Macauley SL, Holtzman DM | EBioMedicine | 2015 | 0 |
Debates (20)
Multi-agent debates referencing this entity
Investigate how microglial senescence drives ALS progression through inflammatio
closed · Rounds: 4 · Score: 0.50 · 2026-04-26
Hypothesis debate: PLCG2 Allosteric Modulation as a Precision Therapeutic for TR
closed · Rounds: 4 · Score: 0.50 · 2026-04-26
Hypothesis debate: PLCG2 Allosteric Modulation as a Precision Therapeutic for TR
closed · Rounds: 4 · Score: 0.50 · 2026-04-26
Hypothesis debate: Closed-loop optogenetic targeting PV interneurons to restore
closed · Rounds: 4 · Score: 0.50 · 2026-04-26
Hypothesis debate: Closed-loop transcranial focused ultrasound targeting EC-II S
closed · Rounds: 4 · Score: 0.50 · 2026-04-26
Hypothesis debate: TREM2-Dependent Microglial Senescence Transition
closed · Rounds: 4 · Score: 0.64 · 2026-04-26
Hypothesis debate: TREM2-Dependent Astrocyte-Microglia Cross-talk in Neurodegene
closed · Rounds: 4 · Score: 0.50 · 2026-04-26
Hypothesis debate: Closed-loop transcranial focused ultrasound with 40Hz gamma e
closed · Rounds: 4 · Score: 0.50 · 2026-04-26
What are the key mechanistic, therapeutic, and diagnostic dimensions of TREM2 in
closed · Rounds: 4 · Score: 0.92 · 2026-04-26
What are the mechanisms by which microglial senescence contributes to ALS pathol
closed · Rounds: 6 · Score: 0.75 · 2026-04-26
Related Research
Hypotheses and analyses mentioning TREM2 in their description or question text
SIRT1-Mediated Reversal of TREM2-Dependent Microglial Senescence
Score: 0.893 · neurodegeneration · 2026-04-12
## Mechanistic Overview SIRT1-Mediated Reversal of TREM2-Dependent Microglial Senescence starts from the claim that modu
TREM2-Mediated Astrocyte-Microglia Crosstalk in Neurodegeneration
Score: 0.892 · neurodegeneration · 2026-04-07
## Mechanistic Overview TREM2-Mediated Astrocyte-Microglia Crosstalk in Neurodegeneration starts from the claim that mod
TREM2-APOE Axis Dissociation for Selective DAM Activation
Score: 0.886 · neurodegeneration · 2026-04-16
## Mechanistic Overview TREM2-APOE Axis Dissociation for Selective DAM Activation starts from the claim that modulating
TREM2 R47H Variant-Driven Metabolic Dysfunction as the Primary Trigger for Faile
Score: 0.862 · neurodegeneration · 2026-04-16
## Mechanistic Overview TREM2 R47H Variant-Driven Metabolic Dysfunction as the Primary Trigger for Failed DAM Transition
TREM2-Mediated Microglial Dysfunction Disrupts Perivascular Tau Clearance
Score: 0.861 · neuroscience · 2026-04-12
## Mechanistic Overview TREM2-Mediated Microglial Dysfunction Disrupts Perivascular Tau Clearance starts from the claim
Microglial Senescence Prevention via TREM2/SASP Axis
Score: 0.837 · neurodegeneration · 2026-04-17
## Mechanistic Overview Microglial Senescence Prevention via TREM2/SASP Axis starts from the claim that modulating not y
TREM2-Deficient Microglia as Drivers of Amyloid Plaque Toxicity in Alzheimer's D
Score: 0.827 · neurodegeneration · 2026-04-26
TREM2 loss-of-function variants impair microglial survival, clustering around amyloid plaques, and phagocytic clearance,
Microglial-Mediated Tau Clearance Dysfunction via TREM2 Signaling
Score: 0.827 · neuroscience · 2026-04-07
## Mechanistic Overview Microglial-Mediated Tau Clearance Dysfunction via TREM2 Signaling starts from the claim that mod
Rare TREM2-TYROBP pathway variants complement standard PRS by identifying microg
Score: 0.000 · Late-onset Alzheimer's disease · 2026-04-26
We hypothesize that rare loss-of-function variants in microglial-expressed genes within the TREM2-TYROBP signaling casca
AD fine-mapping identifies causal variants in microglia-specific enhancers with
Score: 0.000 · Alzheimer's disease · 2026-04-26
Bayesian fine-mapping of the top 25 AD GWAS loci will identify credible sets significantly enriched for variants disrupt
CSF TREM2 Fragment Ratio Integrated with Neuroinflammatory Cascade Markers
Score: 0.000 · biomarkers · 2026-04-27
Site-specific TREM2 cleavage fragments (N-terminal vs C-terminal ratios) serve as the primary readout for microglial pri
Astrocytic TREM2-Like Receptor Modulation of Synaptic Strengthening Pathways
Score: 0.000 · connectomics · 2026-04-27
This hypothesis proposes that astrocytic TREM2-like receptors (TREML2) regulate synaptic plasticity through a fundamenta
TREM2-Dependent Astrocyte-Microglia Cross-talk in Neuroinflammation
Score: 0.000 · neurodegeneration · 2026-04-27
TREM2-Dependent Astrocyte-Microglia Cross-talk in Neuroinflammation proposes that TREM2 dysfunction disrupts critical in
Plasma TREM2 Ectodomain Glycosylation Patterns as Microglial Senescence Biomarke
Score: 0.000 · biomarkers · 2026-04-27
Site-specific glycosylation patterns on circulating TREM2 ectodomain fragments distinguish senescent from activated micr
Site-Specific TREM2 Fragment Analysis Within Multi-Analyte CSF Panel for Microgl
Score: 0.000 · biomarkers · 2026-04-26
This hypothesis proposes that incorporating Parent B's mechanistically precise site-specific TREM2 fragment ratio analys