concept

DAM

Entity Detail — Knowledge Graph Node

Understanding Entity Pages

This page aggregates everything SciDEX knows about DAM: 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.

31Connections

30Hypotheses

15Analyses

19Outgoing

12Incoming

15Experiments

17Debates

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💡 Concept Info

Name	DAM
Key Genes/Proteins	AMYLOID, APOE
Related Diseases	ALZHEIMERS, Alzheimer's Disease, MITOPHAGY, NEURODEGENERATION
Linked Hypotheses	18 hypotheses

Wiki Pages (21)

Knowledge base pages for this entity

Canonical Page

Pathway Diagram

graph TD
    DAM["DAM"]
    DAM -->|"component_of"| Microglia["Microglia"]
    DAM -->|"interacts"| Amyloid_Beta["Amyloid Beta"]
    DAM -.protects against.-> Neurodegeneration["Neurodegeneration"]
    DAM -->|"involved_in"| Phagocytosis["Phagocytosis"]
    DAM -->|"involved_in"| Alzheimer_s_Disease["Alzheimer's Disease"]
    DAM -->|"mediates"| Amyloid_Beta_Phagocytosis["Amyloid-Beta Phagocytosis"]
    DAM -->|"expressed in"| CNS["CNS"]
    TREM2["TREM2"] -->|"activates"| DAM

Outgoing (19)

Target	Relation	Type	Str
Alzheimer's Disease	associated_with	disease	0.95
Alzheimer's Disease	associated_with	disease	0.95
Microglia	component_of	cell_type	0.95
Neurodegenerative Diseases	associated_with	disease	0.90
Phagocytosis	involved_in	process	0.90
Neurodegeneration	protects_against	process	0.85
microglia	associated_with	cell_type	0.85
Neurodegeneration	protects_against	process	0.85
Phagocytosis	involved_in	process	0.85
Amyloid-Beta Phagocytosis	mediates	process	0.80
NEURODEGENERATION	associated_with	phenotype	0.72
ALZHEIMERS	associated_with	disease	0.72
CNS	expressed_in	brain_region	0.68
AMYLOID	causes	protein	0.65
TREM2	causes	gene	0.65
TREM2	regulates	gene	0.65
SYK	activates	gene	0.65
SYK	interacts_with	gene	0.65
APOE	interacts_with	gene	0.64

Incoming (12)

Source	Relation	Type	Str
TREM2	activates	protein	0.87
ASTROCYTES	treats	cell_type	0.65
APOE	activates	gene	0.65
NEUROINFLAMMATION	causes	phenotype	0.65
MICROGLIA	interacts_with	cell_type	0.65
MITOPHAGY	protects_against	phenotype	0.65
FRONTAL CORTEX	associated_with	brain_region	0.45
HIPPOCAMPUS	associated_with	brain_region	0.45
CORTEX	associated_with	brain_region	0.45
VORINOSTAT	associated_with	drug	0.45
NLRP3 INFLAMMASOME	associated_with	pathway	0.45
TREM2-APOE axis	co_associated_with	gene	0.30

Targeting Hypotheses (30)

Hypotheses where this entity is a therapeutic target

Hypothesis	Score	Disease	Analysis
HK2-Dependent Metabolic Checkpoint as the Gatekeeper of DAM	0.919	neurodegeneration	How do different microglial subtypes (DA
Multi-Target Hypothesis: Aβ-Induced Cholinergic Damage is Pa	0.887	-	Do β-amyloid plaques and neurofibrillary
TREM2-APOE Axis Dissociation for Selective DAM Activation	0.886	neurodegeneration	TREM2 agonism vs antagonism in DAM micro
TREM2 R47H Variant-Driven Metabolic Dysfunction as the Prima	0.858	neurodegeneration	How do different microglial subtypes (DA
Mitochondrial DAMPs-Driven AIM2 Inflammasome Activation in N	0.805	neurodegeneration	What are the mechanisms by which gut mic

Cell-Type Specific TREM2 Upregulation in DAM Microglia	0.761	Alzheimer's Disease	SEA-AD Gene Expression Profiling — Allen
TREM2-APOE4 Axis Drives Metabolic Inflexibility in DAM	0.720	Alzheimer's disease	-
DAMP-Scavenging Microglial Reset	0.701	-	Neuroinflammation and microglial priming
TREM2-APOE Axis Manipulation via APOE Lipidation for DAM Rec	0.685	neurodegeneration	Microglial subtypes in neurodegeneration
TREM2 Agonism Has Narrow Early-Window at DAM1→DAM2 Transitio	0.668	neurodegeneration	What is the optimal therapeutic window f
PARP1 Inhibition Blocks Poly(PR)-Triggered DNA Damage and Su	0.661	neurodegeneration	What upstream mechanisms trigger p53 act
SPP1+ DAM as Source of Autoimmunity in Neurodegeneration	0.660	Alzheimer's disease	-
Mitochondrial ROS from complex I and cardiolipin instability	0.640	neurodegeneration	What mechanisms drive the self-amplifyin
HBOT at 1.5 ATA for 60 min induces hormetic response via Nrf	0.640	neurodegeneration	What are the optimal oxygen pressure, du
Stage-Selective TREM2 Agonism — Boosting DAM Phagocytosis in	0.637	Alzheimer's disease	TREM2 agonism vs antagonism in DAM micro
Microglial TREM2 downregulation impairs damage-associated re	0.628	Alzheimer's disease	SEA-AD Single-Cell Analysis: Cell-Type V
TREM2 Super-Agonist Induction of DAM Program	0.627	neurodegeneration	Analyze the spectrum of microglial activ
Microglial Priming via NF-κB-Dependent DAM Phenotype and Com	0.580	neuroinflammation	How does sevoflurane-induced NF-κB activ
Disease-Associated Microglia (DAM) Program Drives IBA1 Downr	0.571	neuroinflammation	What causes IBA1 low/negative microglia
P2Y6R activation by UDP from damaged neurons drives microgli	0.540	neurodegeneration	Which tau propagation mechanism predomin
Soluble CX3CL1 cleavage by ADAM proteases disengages fractal	0.540	neurodegeneration	Synaptic pruning by microglia in neurode
PI3P Generation at Damaged Lysosomes Promotes Membrane Repai	0.530	neurodegeneration	How does controlled lysosomal membrane p
Telomere Attrition and DNA Damage Response Activation Induce	0.520	neurodegeneration	What molecular mechanisms drive microgli
Mitochondrial DNA Damage and cGAS-STING Activation Induces M	0.520	neurodegeneration	What molecular mechanisms drive microgli
TYRO3-STAT1 Axis to Preserve Parvalbumin Interneuron Functio	0.506	neuroinflammation	Why do TAM receptors protect against neu
Microglial Priming Window for HDAC1-Dependent DAM Transition	0.463	neurodegeneration	What is the optimal therapeutic window d
Mitochondrial Damage-Triggered SPP1 Inflammasome Coupling	0.453	neuroinflammation	What molecular mechanisms mediate SPP1-i
MITF Acts as the Primary Transcriptional Effector Downstream	0.444	neurodegeneration	How does HDAC1/2 deletion specifically e
DNA Damage Repair Dysfunction Creating TDP-43 Pathology Feed	0.430	neurodegeneration	How does APOE4 mechanistically increase
ITGAX/CD11c Targeting to Eliminate Pro-inflammatory DAM in A	0.408	neurodegeneration	Microglial subtypes in neurodegeneration

Mentioning Analyses (15)

Scientific analyses that reference this entity

Microglial subtypes in neurodegeneration — friend vs foe

neurodegeneration | 2026-04-17 | 7 hypotheses Top: 0.685

Analyze the spectrum of microglial activation states (DAM, homeostatic, inflamma

neurodegeneration | 2026-04-17 | 0 hypotheses

Analyze the spectrum of microglial activation states (DAM, homeostatic, inflamma

neurodegeneration | 2026-04-16 | 1 hypotheses Top: 0.627

Do these mechanistic hypotheses from the SEA-AD Atlas bundle explain layer-speci

neurodegeneration | 2026-04-10 | 0 hypotheses

Do these mechanistic hypotheses explain layer-specific synaptic vulnerability in

neurodegeneration | 2026-04-10 | 0 hypotheses

Experiments (15)

Experimental studies targeting or related to this entity

Experiment	Type	Disease	Score	Feasibility	Model	Status	Est. Cost
Anti-ASC antibody intracerebroventricular injection in APP/PS1 mice	validation	Alzheimer's disease	0.950	0.00	APP/PS1 transgenic mice (8 mon	proposed	N/A
Curcumin-Licorice Combination in D-galactose/Sodium Nitrite AD Model	validation	Alzheimer's disease	0.950	0.00	C57BL/6 mice	proposed	N/A
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
SPP1 upregulation in perivascular cells in AD mouse models	exploratory	Alzheimer's disease	0.900	0.00	AD mouse models	proposed	N/A
Tet2 modulation in Aβ42-injured mouse hippocampal neurons	exploratory	Alzheimer's disease	0.900	0.00	primary mouse hippocampal neur	proposed	N/A
AAV-mediated Tet2 modulation in 2×Tg-AD mice behavioral study	validation	Alzheimer's disease	0.900	0.00	young APPswe/PSEN1 double-tran	proposed	N/A
Cerebrovascular function analysis in CD2AP mutant mice	validation	Alzheimer's disease	0.900	0.00	mice	proposed	N/A
Cerebral blood flow regulation in CD2AP mutant mice	validation	Alzheimer's disease	0.880	0.00	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
Abeta-induced cell death and aggregation in GD3S-deficient neurons	exploratory	Alzheimer's disease	0.850	0.00	primary neurons and astrocytes	proposed	N/A
Generation of Aβ-specific Tregs using CRISPR-Cas9	exploratory	Alzheimer's disease	0.850	0.00	engineered Tregs	proposed	N/A
Cell-cell interaction analysis of perivascular-microglial crosstalk	exploratory	Alzheimer's disease	0.800	0.00	AD mouse models	proposed	N/A
Microglial Aging and Immune Memory in Neurodegeneration — Training the	validation	Alzheimer's Disease	0.400	0.50	human	proposed	$2,960,000

Related Papers (20)

Scientific publications cited in analyses involving this entity

Title & PMID	Authors	Journal	Year	Citations
Transcriptomic cytoarchitecture reveals principles of human neocortex organizati [PMID:37824655]	Jorstad NL, Close J, Johansen N, Yanny A	Science	2023	186
Integrated multimodal cell atlas of Alzheimer’s disease [PMID:37292694]	Gabitto MI, Travaglini KJ, Rachleff VM,	Research Square	2023	63
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
Moderate Effects of the Arginine to Histidine R47H Variant of the Triggering Rec [PMID:41890852]	["Ramirez G", "Hernandez D", "Teal A", "	Research square	2026	0
Increased plasma soluble TREM2 levels in non-Alzheimer's dementia. [PMID:41920402]	Güven Gamze; Gezegen Haşim; &	Acta neurologica Belgica	2026	0
AI-guided design of cyclic peptide binders targeting TREM2 using CycleRFdiffusio [PMID:41435973]	Cho S, Zhu R, Kuncewicz K, Duan H, Gabr	Bioorg Med Chem Lett	2026	0
ITAM-Syk signaling mediates the rebound phenomenon after anti-RANKL antibody dis [PMID:41490759]	Ishizu H, Hasegawa T, Shimizu T, Yamamot	Bone	2026	0
Oxaliplatin-artesunate conjugate intensifies suppression on colorectal cancer by [PMID:41520444]	Tan Y, Yang T, Jiang S, Li S, Cai L et a	J Inorg Biochem	2026	0
Loss of Triggering Receptor Expressed on Myeloid Cells 2 Impairs Microglial Func [PMID:41643896]	Chen G, Wang Z, Zhao C, Wang C, Li Y et	Am J Pathol	2026	0
Microglial metabolic reprogramming in Alzheimer's disease: Pathways, mechanisms, [PMID:41651180]	Yang FG, Yang H, Han SW, Wang JT, Gao W	Ageing Res Rev	2026	0
Plant-derived bioactive compounds modulate the gut microbiota in Alzheimer's dis [PMID:41678917]	Xue D, Hu X, Li R, Sun T, Qian S et al.	Phytomedicine	2026	0
Triggering Receptor Expressed on Myeloid Cells-2 Regulates Innate Lymphoid Cell [PMID:41928407]	Shen HC, Chen NJ, Sun CY, Yu WK, Su VY e	Kaohsiung J Med Sci	2026	0
TREM2 deficiency delays postnatal microglial maturation and synaptic pruning, le [PMID:41930604]	Yang HC, Deng YS, Zhang J, Zhang T, Song	J Alzheimers Dis	2026	0
Population-scale burden analysis of rare damaging coding variants identifies nov [PMID:41867223]	Le Guen Y, Peña-Tauber A, Pulgrossi RC,	medRxiv : the preprint server	2026	0
TREM2 as a possible link between Alzheimer's disease and diabetes mellitus. [PMID:41862118]	Chen W, Huang N, Huang W, Wang M, Luo Y,	Experimental neurology	2026	0
The microglial TREM2 receptor programs hippocampal development in a mouse model [PMID:41887542]	Ahmed S, Bowers C, Munoz-Martin J, Jamwa	Brain, behavior, and immunity	2026	0
Neuroinflammation and Alzheimer's disease: Unravelling the molecular mechanisms. [PMID:40938771]	Kakkar A, Singh H, Singh BK, Kumar A, Mi	Journal of Alzheimer's disease	2025	0
Dehydroervatamine as a promising novel TREM2 agonist, attenuates neuroinflammati [PMID:39609160]	Li L, Xu N, He Y, Tang M, Yang B, Du J,	Neurotherapeutics : the journa	2025	0
TREM2 regulates microglial lipid droplet formation and represses post-ischemic b [PMID:38042110]	Wei W, Zhang L, Xin W, Pan Y, Tatenhorst	Biomedicine & pharmacotherapy	2024	0
Defects in lysosomal function and lipid metabolism in human microglia harboring [PMID:37115208]	Filipello F, You SF, Mirfakhar FS, Mahal	Acta neuropathologica	2023	0

Debates (17)

Multi-agent debates referencing this entity

Mechanistic validation of SEA-AD differential expression hypotheses: Complement

closed · Rounds: 0 · Score: 0.66 · 2026-04-21

Mechanistic validation of SEA-AD differential expression hypotheses: Complement

closed · Rounds: 0 · Score: 0.64 · 2026-04-21

Do these mechanistic hypotheses explain layer-specific synaptic vulnerability in

closed · Rounds: 4 · Score: 0.30 · 2026-04-21

Do these mechanistic hypotheses from the SEA-AD Atlas bundle explain layer-speci

closed · Rounds: 4 · Score: 0.30 · 2026-04-21

Analyze the spectrum of microglial activation states (DAM, homeostatic, inflamma

closed · Rounds: 4 · Score: 0.50 · 2026-04-20

Analyze the spectrum of microglial activation states (DAM, homeostatic, inflamma

closed · Rounds: 4 · Score: 0.50 · 2026-04-18

Analyze the spectrum of microglial activation states (DAM, homeostatic, inflamma

closed · Rounds: 4 · Score: 0.50 · 2026-04-18

How does microglial priming contribute to early Alzheimer's disease pathology? F

closed · Rounds: 4 · Score: 0.80 · 2026-04-12

TREM2 Therapeutic Strategy Post-INVOKE-2

closed · Rounds: 4 · Score: 0.93 · 2026-04-06

Neuroinflammation and microglial priming in early AD

closed · Rounds: 3 · Score: 0.95 · 2026-04-04

Related Research

Hypotheses and analyses mentioning DAM in their description or question text

Cell-Type Specific TREM2 Upregulation in DAM Microglia

Score: 0.761 · Alzheimer's Disease · 2026-04-02

## Mechanistic Overview Cell-Type Specific TREM2 Upregulation in DAM Microglia starts from the claim that modulating TRE

DAMP-Scavenging Microglial Reset

Score: 0.701 · unknown disease · 2026-04-04

## Mechanistic Overview DAMP-Scavenging Microglial Reset starts from the claim that modulating HMGB1, S100 proteins with

TREM2-APOE Axis Manipulation via APOE Lipidation for DAM Recruitment

Score: 0.685 · neurodegeneration · 2026-04-25

Strongest mechanistic support among all hypotheses. TREM2-TYROBP signaling for DAM transition well-established. AL002 Ph

TREM2 Agonism Has Narrow Early-Window at DAM1→DAM2 Transition Checkpoint

Score: 0.668 · neurodegeneration · 2026-04-22

**Molecular Mechanism and Rationale** The triggering receptor expressed on myeloid cells 2 (TREM2) serves as a critical

PARP1 Inhibition Blocks Poly(PR)-Triggered DNA Damage and Subsequent p53 Activat

Score: 0.661 · neurodegeneration · 2026-04-15

## Mechanistic Overview PARP1 Inhibition Blocks Poly(PR)-Triggered DNA Damage and Subsequent p53 Activation starts from

Mitochondrial ROS from complex I and cardiolipin instability forms a local organ

Score: 0.640 · neurodegeneration · 2026-04-25

Electron leak at complex I and destabilized inner-membrane architecture generate superoxide and lipid oxidation that dam

HBOT at 1.5 ATA for 60 min induces hormetic response via Nrf2 activation, enhanc

Score: 0.640 · neurodegeneration · 2026-04-25

This hypothesis posits that mild hyperbaric oxidative stress activates Nrf2-ARE transcriptional programs, upregulating S

Stage-Selective TREM2 Agonism — Boosting DAM Phagocytosis in Early Amyloid Phase

Score: 0.637 · Alzheimer's disease · 2026-04-04

## Mechanistic Overview Stage-Selective TREM2 Agonism — Boosting DAM Phagocytosis in Early Amyloid Phase starts from the

Microglial TREM2 downregulation impairs damage-associated response in late-stage

Score: 0.628 · Alzheimer's disease · 2026-04-04

## Mechanistic Overview Microglial TREM2 downregulation impairs damage-associated response in late-stage Alzheimer's dis

TREM2 Super-Agonist Induction of DAM Program

Score: 0.627 · neurodegeneration · 2026-04-21

## **Molecular Mechanism and Rationale** The triggering receptor expressed on myeloid cells 2 (TREM2) represents a crit

Microglial Priming via NF-κB-Dependent DAM Phenotype and Complement Biosynthesis

Score: 0.580 · neuroinflammation · 2026-04-21

**Molecular Mechanism and Rationale** The nuclear factor kappa B (NF-κB) signaling pathway represents a critical molecu

Disease-Associated Microglia (DAM) Program Drives IBA1 Downregulation

Score: 0.571 · neuroinflammation · 2026-04-21

## Mechanistic Overview Disease-Associated Microglia (DAM) Program Drives IBA1 Downregulation starts from the claim that

P2Y6R activation by UDP from damaged neurons drives microglial phagocytosis and

Score: 0.540 · neurodegeneration · 2026-04-21

## Mechanistic Overview P2Y6R activation by UDP from damaged neurons drives microglial phagocytosis and exosomal re-secr

DAM

Understanding Entity Pages

Wiki Pages (21)

Disease-Associated Microglia (DAM)

ADAM15 Protein

ADAM22 — ADAM Metallopeptidase Domain 22

ADAM23 Gene

ADAM10 — A Disintegrin And Metalloproteinase Domain 10

ADAM12 Gene

Disease-Associated [Microglia](/cell-types/microglia-neuroinflammation) (DAM)

ADAM8 Gene

ADAMTS13 Gene

ADAM17 Protein

Disease-Associated Microglia (DAM)

ADAMTS4 Gene

ADAMTS-4 Protein

Disease-Associated Microglia (DAM)

Disease-Associated Microglia Type 2 (DAM2)

ADAM19 Gene

ADAM15 Gene

ADAM10 Protein

ADAM23 Protein

ADAM12 Protein

ADAM22 Protein

Pathway Diagram

Outgoing (19)

Incoming (12)

Targeting Hypotheses (30)

Mentioning Analyses (15)

Microglial subtypes in neurodegeneration — friend vs foe

Analyze the spectrum of microglial activation states (DAM, homeostatic, inflamma

Analyze the spectrum of microglial activation states (DAM, homeostatic, inflamma

Do these mechanistic hypotheses from the SEA-AD Atlas bundle explain layer-speci

Do these mechanistic hypotheses explain layer-specific synaptic vulnerability in

Mechanistic validation of SEA-AD differential expression hypotheses: Complement

TREM2 Therapeutic Strategy Post-INVOKE-2

Neuroinflammation and microglial priming in early AD

Neuroinflammation and microglial priming in early Alzheimer's Disease

Immune atlas neuroinflammation analysis in neurodegeneration

Cell type vulnerability in Alzheimers Disease (SEA-AD transcriptomic data)

TREM2 agonism vs antagonism in DAM microglia

Immune atlas neuroinflammation analysis in neurodegeneration

Microglial subtypes in neurodegeneration — friend vs foe

TREM2 agonism vs antagonism in DAM microglia

Experiments (15)

Related Papers (20)

Debates (17)

Mechanistic validation of SEA-AD differential expression hypotheses: Complement

Mechanistic validation of SEA-AD differential expression hypotheses: Complement

Do these mechanistic hypotheses explain layer-specific synaptic vulnerability in

Do these mechanistic hypotheses from the SEA-AD Atlas bundle explain layer-speci

Analyze the spectrum of microglial activation states (DAM, homeostatic, inflamma

Analyze the spectrum of microglial activation states (DAM, homeostatic, inflamma

Analyze the spectrum of microglial activation states (DAM, homeostatic, inflamma

How does microglial priming contribute to early Alzheimer's disease pathology? F

TREM2 Therapeutic Strategy Post-INVOKE-2

Neuroinflammation and microglial priming in early AD

Related Research

Cell-Type Specific TREM2 Upregulation in DAM Microglia

DAMP-Scavenging Microglial Reset

TREM2-APOE Axis Manipulation via APOE Lipidation for DAM Recruitment

TREM2 Agonism Has Narrow Early-Window at DAM1→DAM2 Transition Checkpoint

PARP1 Inhibition Blocks Poly(PR)-Triggered DNA Damage and Subsequent p53 Activat

Mitochondrial ROS from complex I and cardiolipin instability forms a local organ

HBOT at 1.5 ATA for 60 min induces hormetic response via Nrf2 activation, enhanc

Stage-Selective TREM2 Agonism — Boosting DAM Phagocytosis in Early Amyloid Phase

Microglial TREM2 downregulation impairs damage-associated response in late-stage

TREM2 Super-Agonist Induction of DAM Program

Microglial Priming via NF-κB-Dependent DAM Phenotype and Complement Biosynthesis

Disease-Associated Microglia (DAM) Program Drives IBA1 Downregulation

P2Y6R activation by UDP from damaged neurons drives microglial phagocytosis and