concept

TDP-43 PATHOLOGY

Entity Detail — Knowledge Graph Node

Understanding Entity Pages

This page aggregates everything SciDEX knows about TDP-43 PATHOLOGY: 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.

56Connections

6Hypotheses

11Analyses

30Outgoing

26Incoming

0Experiments

15Debates

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💡 Concept Info

Name	TDP-43 PATHOLOGY

Pathway Diagram

graph TD
    TDP_43_PATHOLOGY["TDP-43 PATHOLOGY"]
    TDP_43_PATHOLOGY -.biomarker for.-> Amyotrophic_Lateral_Sclerosis["Amyotrophic Lateral Sclerosis"]
    TDP_43_PATHOLOGY -.biomarker for.-> Frontotemporal_Lobar_Degenerat["Frontotemporal Lobar Degeneration"]
    TDP_43_PATHOLOGY -.biomarker for.-> Alzheimer_s_Disease["Alzheimer's Disease"]
    TDP_43_PATHOLOGY -->|"correlates_with"| Cognitive_Decline["Cognitive Decline"]
    TDP_43_PATHOLOGY -->|"expressed in"| Hippocampus["Hippocampus"]
    Plasma_Ev_Tdp_43_Levels["Plasma Ev Tdp-43 Levels"] -.biomarker for.-> TDP_43_PATHOLOGY
    ATXN2["ATXN2"] -->|"contributes to"| TDP_43_PATHOLOGY
    APOE["APOE"] -->|"risk_factor_for"| TDP_43_PATHOLOGY
    APOE4["APOE4"] -->|"risk_factor_for"| TDP_43_PATHOLOGY
    STMN2["STMN2"] -.biomarker for.-> TDP_43_PATHOLOGY
    UNC13A["UNC13A"] -.biomarker for.-> TDP_43_PATHOLOGY
    RIPK1["RIPK1"] -->|"promotes"| TDP_43_PATHOLOGY

Outgoing (30)

Target	Relation	Type	Str
Frontotemporal Lobar Degeneration	biomarker_for	disease	0.95
Amyotrophic Lateral Sclerosis	biomarker_for	disease	0.95
Alzheimer's Disease	associated_with	disease	0.92
Cognitive Impairment	associated_with	phenotype	0.90
cGAS-STING pathway	associated_with	pathway	0.90
mtDNA release	causes	mechanism	0.90
axonal NAD+ metabolism	disrupts	pathway	0.90
Alzheimer's Disease	biomarker_for	disease	0.90
Neurofibrillary Tangles	associated_with	biomarker	0.85
Hippocampal Sclerosis	associated_with	disease	0.85
Cognitive Impairment	associated_with	phenotype	0.85
cognitive decline in Alzheimer's patients	causes	disease	0.85
Cognitive Decline	correlates_with	phenotype	0.85
Alzheimer's Disease severity	drives	phenotype	0.83
Hippocampus	expressed_in	brain_region	0.82
Cognitive Impairment	causes	symptom	0.80
Hippocampal Sclerosis	associated_with	disease	0.78
distal axon vulnerability	associated_with	phenotype	0.70
neuroinflammation	causes	phenotype	0.70
microglial activation (DAM/MGnD)	causes	cell_type	0.70
synaptic loss	causes	phenotype	0.70
local protein synthesis at synapses	impairs	process	0.70
astrocyte homeostasis	disrupts	process	0.70
nucleocytoplasmic transport disruption	causes	mechanism	0.70
mitochondrial dysfunction	causes	mechanism	0.70
microglial activation	activates	process	0.70
axonal injury	causes	mechanism	0.70
mitochondrial calcium buffering impairment	causes	mechanism	0.70
cGAS/STING activation	causes	phenotype	0.70
Microglial senescence	causes	process	0.50

Incoming (26)

Source	Relation	Type	Str
Plasma Ev Tdp-43 Levels	biomarker_for	biomarker	0.94
37415197	observed in	paper	0.90
Ataxin-2 Reduction	associated_with	mechanism	0.90
Nuclear Pore Complex Dysfunction	causes	mechanism	0.90
ATXN2	associated_with	gene	0.90
37777806	worsens	paper	0.90
APOE	risk_factor_for	gene	0.90
APOE4	risk_factor_for	gene	0.88
STMN2	biomarker_for	gene	0.88
UNC13A	biomarker_for	gene	0.88
RIPK1	promotes	protein	0.85
CGAS	associated_with	gene	0.80
APOE4	associated_with	gene	0.80
Aβ42 accumulation	associated_with	protein	0.70
STAT1	associated_with	protein	0.70
IL-1β	associated_with	protein	0.70
TMEM106B	regulates	gene	0.70
mitochondrial fission	early_event	process	0.70
STAT1 activation	associated_with	process	0.70
APOE4	risk_factor_for	gene	0.70
IL-1β	biomarker_for	biomarker	0.70
microglia	modulates	cell_type	0.70
37777806	contributes to	paper	0.60
NRF2 activators	therapeutic_target_for	drug	0.50
IL-6	associated_with	protein	0.50
TNF-α	associated_with	protein	0.50

Targeting Hypotheses (6)

Hypotheses where this entity is a therapeutic target

Hypothesis	Score	Disease	Analysis
C9orf72 ASO Treatment Reverses TDP-43 Pathology in ALS/FTD	0.720	neurodegeneration	Test Hypothesis Fixtures
TDP-43 Pathology Disrupts the HGS-PYGB Autophagy Receptor Ca	0.703	neurodegeneration	What mechanisms underlie neuronal resist
Glial Neuroinflammatory Amplification by TDP-43 Pathology	0.680	neurodegeneration	What mechanisms underlie TDP-43's contri
Necroptosis-cGAS Feedforward Loop Converts TDP-43 Pathology	0.460	neuroinflammation	How does chronic cGAS/STING activation d
DNA Damage Repair Dysfunction Creating TDP-43 Pathology Feed	0.430	neurodegeneration	How does APOE4 mechanistically increase

TDP-43 Pathology Creates a Distinct Epigenetic Clock "Signat	0.387	-	Epigenetic clocks as biomarkers for Alzh

Mentioning Analyses (11)

Scientific analyses that reference this entity

Oxidative Stress Upstream of TDP-43 Mislocalization in ALS Motor Neurons

neurodegeneration | 2026-04-27 | 0 hypotheses

What are the mechanisms by which microglial senescence contributes to ALS pathol

neurodegeneration | 2026-04-26 | 12 hypotheses Top: 0.878

Survival Analysis of AD Patient Cohorts: Prognostic Markers and Time-to-Dementia

neurodegeneration | 2026-04-16 | 3 hypotheses Top: 0.895

What molecular mechanisms enable functional recovery and muscle re-innervation a

neurodegeneration | 2026-04-14 | 2 hypotheses Top: 0.683

What mechanisms underlie TDP-43's contribution to cognitive impairment severity

neurodegeneration | 2026-04-08 | 5 hypotheses Top: 0.680

Experiments (0)

Experimental studies targeting or related to this entity

Experiment	Type	Disease	Score	Feasibility	Model	Status	Est. Cost
No experiments found

Related Papers (10)

Scientific publications cited in analyses involving this entity

Title & PMID	Authors	Journal	Year
TDP-43 seeding induces cytoplasmic aggregation heterogeneity and nuclear loss of [PMID:40157356]	Rummens Jens; Khalil Bilal; Yıld&#	Neuron	2025
TDP-43 seeding induces cytoplasmic aggregation heterogeneity and nuclear loss of [PMID:40157356]	["Rummens Jens", "Khalil Bilal", "Y\u013	Neuron	2025
The new missense G376V-TDP-43 variant induces late-onset distal myopathy but not [PMID:38079474]	Zibold, Lessard, Picard, da Silva, Zador	Brain : a journal of neurology	2024
TDP-43 nuclear condensation and neurodegenerative proteinopathies. [PMID:39327159]	Vassallu, Igaz	Trends in neurosciences	2024
TDP-43 nuclear condensation and neurodegenerative proteinopathies. [PMID:39327159]	Unknown	Trends in neurosciences	2024
The new missense G376V-TDP-43 variant induces late-onset distal myopathy but not [PMID:38079474]	Unknown	Brain : a journal of neurology	2024
Disease-linked TDP-43 hyperphosphorylation suppresses TDP-43 condensation and ag [PMID:35112738]	Gruijs da Silva LA, Simonetti F, Hutten	The EMBO journal	2022
Disease-linked TDP-43 hyperphosphorylation suppresses TDP-43 condensation and ag [PMID:35112738]	Gruijs da Silva LA, Simonetti F, Hutten	The EMBO journal	2022
FUS and TDP-43 Phases in Health and Disease. [PMID:33446423]	["Portz Bede", "Lee Bo Lim", "Shorter Ja	Trends in biochemical sciences	2021
FUS and TDP-43 Phases in Health and Disease. [PMID:33446423]	["Portz Bede", "Lee Bo Lim", "Shorter Ja	Trends in biochemical sciences	2021

Debates (15)

Multi-agent debates referencing this entity

Can targeting oxidative stress pathways (NRF2, SOD1, mitochondrial ROS) upstream

closed · Rounds: 6 · Score: 0.62 · 2026-04-27

Debate: TBK1 Loss Locks Microglia in an Aged/Senescent Transcriptional State, Fu

closed · Rounds: 4 · Score: 0.33 · 2026-04-27

Investigate how microglial senescence drives ALS progression through inflammatio

closed · Rounds: 4 · Score: 0.50 · 2026-04-26

What are the mechanisms by which microglial senescence contributes to ALS pathol

closed · Rounds: 6 · Score: 0.75 · 2026-04-26

While the study establishes TDP-43 triggers mtDNA release via mPTP to activate c

closed · Rounds: 4 · Score: 0.73 · 2026-04-21

The abstract identifies APOE4 association with increased TDP-43 pathology but th

closed · Rounds: 4 · Score: 0.61 · 2026-04-21

The study identifies cGAS/STING activation as a consequence of TDP-43-mediated m

closed · Rounds: 4 · Score: 0.73 · 2026-04-21

TDP-43 inclusions occur in AD, ALS, and FTLD but the pathogenic mechanisms leadi

closed · Rounds: 4 · Score: 0.70 · 2026-04-21

While the study demonstrates TDP-43 triggers mPTP-mediated mtDNA release, the mo

closed · Rounds: 4 · Score: 0.77 · 2026-04-21

AD patients with TDP-43 pathology show worse cognitive impairment, but how TDP-4

closed · Rounds: 4 · Score: 0.73 · 2026-04-21

Related Research

Hypotheses and analyses mentioning TDP-43 PATHOLOGY in their description or question text

TDP-43 Pathology Creates a Distinct Epigenetic Clock "Signature Divergence" Dete

Score: 0.387 · unknown disease · 2026-04-25

Concise Statement: TDP-43 proteinopathy (as seen in LATE — Limbic-predominant Age-related TDP-43 Encephalopathy) genera

TDP-43 PATHOLOGY

Understanding Entity Pages

Pathway Diagram

Outgoing (30)

Incoming (26)

Targeting Hypotheses (6)

Mentioning Analyses (11)

Oxidative Stress Upstream of TDP-43 Mislocalization in ALS Motor Neurons

What are the mechanisms by which microglial senescence contributes to ALS pathol

Survival Analysis of AD Patient Cohorts: Prognostic Markers and Time-to-Dementia

What molecular mechanisms enable functional recovery and muscle re-innervation a

What mechanisms underlie TDP-43's contribution to cognitive impairment severity

What upstream mechanisms cause TDP-43 to trigger mPTP opening and can this be th

What mechanisms drive TDP-43 pathology specifically in Alzheimer's disease versu

How does chronic cGAS/STING activation downstream of TDP-43 contribute to progre

How does APOE4 mechanistically increase TDP-43 pathology frequency in Alzheimer'

What determines the specificity of TDP-43-induced mitochondrial DNA release for

Protein aggregation cross-seeding across neurodegenerative diseases

Experiments (0)

Related Papers (10)

Debates (15)

Can targeting oxidative stress pathways (NRF2, SOD1, mitochondrial ROS) upstream

Debate: TBK1 Loss Locks Microglia in an Aged/Senescent Transcriptional State, Fu

Investigate how microglial senescence drives ALS progression through inflammatio

What are the mechanisms by which microglial senescence contributes to ALS pathol

While the study establishes TDP-43 triggers mtDNA release via mPTP to activate c

The abstract identifies APOE4 association with increased TDP-43 pathology but th

The study identifies cGAS/STING activation as a consequence of TDP-43-mediated m

TDP-43 inclusions occur in AD, ALS, and FTLD but the pathogenic mechanisms leadi

While the study demonstrates TDP-43 triggers mPTP-mediated mtDNA release, the mo

AD patients with TDP-43 pathology show worse cognitive impairment, but how TDP-4

Related Research

TDP-43 Pathology Creates a Distinct Epigenetic Clock "Signature Divergence" Dete