Disease-Associated Microglia (DAM)

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)

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

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-enrichment -->

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

• Unknown (PanglaoDB):

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

• Unknown (PanglaoDB):

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

• 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

• Upregulation of TREM2 and APOE
• Enhanced phagocytosis of pathological α-synuclein
• Potential role in propagating pathology via exosome release

Amyotrophic Lateral Sclerosis (ALS)

• Upregulation of TREM2 pathway genes
• Response to motor neuron degeneration
• Potential dual roles in both protective and detrimental inflammation

Therapeutic Implications

Targeting DAM Pathways

Biomarker Potential

• 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)

• [TREM2 agonism vs antagonism in DAM microglia](/analysis/SDA-2026-04-01-gap-001) &#x1f504;
• [TREM2 agonism vs antagonism in DAM microglia](/analysis/SDA-2026-04-02-gap-001) &#x1f504;

• [TREM2 agonism vs antagonism in DAM microglia](/analysis/SDA-2026-04-01-gap-001) &#x1f504;
• [TREM2 agonism vs antagonism in DAM microglia](/analysis/SDA-2026-04-02-gap-001) &#x1f504;

Pathway Diagram

The following diagram shows the key molecular relationships involving Disease-Associated Microglia (DAM) discovered through SciDEX knowledge graph analysis: