Disease-Associated Microglia (DAM)
Introduction
<table class="infobox infobox-cell">
<tr>
<th class="infobox-header" colspan="2">Disease-Associated Microglia (DAM)</th>
</tr>
<tr>
<td class="label">Taxonomy</td>
<td>ID</td>
</tr>
<tr>
<td class="label">Cell Ontology (CL)</td>
<td>[CL:0000095](https://www.ebi.ac.uk/ols4/ontologies/cl/classes/http%253A%252F%252Fpurl.obolibrary.org%252Fobo%252FCL_0000095)</td>
</tr>
<tr>
<td class="label">Database</td>
<td>ID</td>
</tr>
<tr>
<td class="label">Cell Ontology</td>
<td>[CL:0000095](https://www.ebi.ac.uk/ols4/ontologies/cl/classes/http%253A%252F%252Fpurl.obolibrary.org%252Fobo%252FCL_0000095)</td>
</tr>
<tr>
<td class="label">Cell Ontology</td>
<td>[CL:0000129](https://www.ebi.ac.uk/ols4/ontologies/cl/classes/http%253A%252F%252Fpurl.obolibrary.org%252Fobo%252FCL_0000129)</td>
</tr>
<tr>
<td class="label">Gene</td>
<td>Function</td>
</tr>
<tr>
<td class="label">TREM2</td>
<td>Triggering receptor on myeloid cells 2</td>
</tr>
<tr>
<td class="label">APOE</td>
<td>Apolipoprotein E</td>
</tr>
<tr>
<td class="label">CLEC7A</td>
<td>C-type lectin domain family 7 member A</td>
</tr>
<tr>
<td class="label">ITGAX</td>
<td>CD11c</td>
</tr>
<tr>
<td class="label">CD68</td>
<td>Macrosialin</td>
</tr>
</table>
Disease Associated Microglia (Dam) is a cell type relevant to neurodegenerative disease research. This page covers its role in brain function, involvement in disease processes, and significance for therapeutic strategies.
Overview
Mermaid diagram (expand to render)
Disease-associated microglia (DAM), also known as neurodegenerative disease-associated microglia (NAM), represent a specialized microglial activation state observed in various neurodegenerative conditions including Alzheimer's disease, Parkinson's disease, and ALS. DAM cells adopt a distinct transcriptional profile that differs from both surveilling (homeostatic) microglia and inflammatory (M1) microglia["@kerenshaul2017"][@deczkowska2018].
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Multi-Taxonomy Classification
Taxonomy Database Cross-References
Morphology & Electrophysiology
- Morphology: neuron associated cell (source: Cell Ontology)
- Morphology can be inferred from Cell Ontology classification
PanglaoDB Marker Cross-References
External Database Links
- [Cell Ontology (CL:0000095)](https://www.ebi.ac.uk/ols4/ontologies/cl/classes/http%253A%252F%252Fpurl.obolibrary.org%252Fobo%252FCL_0000095)
- [OBO Foundry (CL:0000095)](http://purl.obolibrary.org/obo/CL_0000095)
- [Allen Brain Cell Atlas](https://portal.brain-map.org/atlases-and-data/bkp/abc-atlas)
- [CellxGene Census](https://cellxgene.cziscience.com/)
- [Human Cell Atlas](https://www.humancellatlas.org/)
- [PanglaoDB](https://panglaodb.se/)
Taxonomy & Classification
PanglaoDB Marker Cross-References
External Database Links
- [Cell Ontology (CL:0000095)](https://www.ebi.ac.uk/ols4/ontologies/cl/classes/http%253A%252F%252Fpurl.obolibrary.org%252Fobo%252FCL_0000095)
- [OBO Foundry (CL:0000095)](http://purl.obolibrary.org/obo/CL_0000095)
- [Allen Brain Cell Atlas](https://portal.brain-map.org/atlases-and-data/bkp/abc-atlas)
- [CellxGene Census](https://cellxgene.cziscience.com/)
- [PanglaoDB](https://panglaodb.se/)
Molecular Signature
Stage 1 DAM Markers
- TREM2-independent activation
- CD86 upregulation
- MHC-II expression increased
- IL-1β production
Stage 2 DAM Markers
- TREM2-dependent pathway activation
- APOE expression
- TGFBI (Transforming Growth Factor Beta Induced)
- LPL (Lipoprotein Lipase)
- CST3 (Cystatin C)
- Tyrobp (TYROBP/DAP12) upregulation
Core DAM Genes
Role in Neurodegeneration
Alzheimer's Disease
In AD, DAM cells cluster around amyloid plaques and adopt a protective phenotype in early disease stages, attempting to clear toxic protein aggregates. However, chronic DAM activation can become maladaptive[@hansen2018]:
- Plaque-associated microglia show DAM signature
- TREM2 variants increase AD risk (R47H, R62H)
- DAM may limit Aβ spread but also contribute to synaptic loss
Parkinson's Disease
In PD and related synucleinopathies, DAM cells respond to α-synuclein aggregates:
- Upregulation of TREM2 and APOE
- Enhanced phagocytosis of pathological α-synuclein
- Potential role in propagating pathology via exosome release
Amyotrophic Lateral Sclerosis (ALS)
DAM-like cells in ALS show:
- Upregulation of TREM2 pathway genes
- Response to motor neuron degeneration
- Potential dual roles in both protective and detrimental inflammation
Therapeutic Implications
Targeting DAM Pathways
TREM2 Agonists - Enhance microglial clearance function
APOE Modulation - Reduce lipid accumulation in microglia
CSF1R Inhibitors - Deplete disease-promoting microglial populationsBiomarker Potential
DAM signatures in CSF or blood may serve as:
- Diagnostic markers for neurodegenerative disease stage
- Pharmacodynamic biomarkers for immunomodulatory therapies
- Cell-Types/Disease-Associated-Microglia-Dam — This page
Background
The study of Disease Associated Microglia (Dam) has evolved significantly over the past decades. Research in this area has revealed important insights into the underlying mechanisms of neurodegeneration and continues to drive therapeutic development.
Historical context and key discoveries in this field have shaped our current understanding and will continue to guide future research directions.
External Links
- [PubMed](https://pubmed.ncbi.nlm.nih.gov/) - Biomedical literature
- [Alzheimer's Disease Neuroimaging Initiative](https://adni.loni.usc.edu/) - Research data
- [Allen Brain Atlas](https://brain-map.org/) - Brain gene expression data
External Links
- [ClinicalTrials.gov - Urolithin A](https://clinicaltrials.gov/search?cond=Alzheimer+OR+Parkinson&intr=Urolithin+A)parkin)
- [Science - Mitophagy and Aging](https://www.science.org/doi/10.1126/science.aan0442)
Related Analyses:
- [TREM2 agonism vs antagonism in DAM microglia](/analysis/SDA-2026-04-01-gap-001) 🔄
- [TREM2 agonism vs antagonism in DAM microglia](/analysis/SDA-2026-04-02-gap-001) 🔄
Related Analyses:
- [TREM2 agonism vs antagonism in DAM microglia](/analysis/SDA-2026-04-01-gap-001) 🔄
- [TREM2 agonism vs antagonism in DAM microglia](/analysis/SDA-2026-04-02-gap-001) 🔄
Pathway Diagram
The following diagram shows the key molecular relationships involving Disease-Associated Microglia (DAM) discovered through SciDEX knowledge graph analysis:
Mermaid diagram (expand to render)