disease

FTD

Entity Detail — Knowledge Graph Node

Understanding Entity Pages

This page aggregates everything SciDEX knows about FTD: 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.

1161Connections

12Hypotheses

13Analyses

50Outgoing

50Incoming

6Experiments

20Debates

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Disease Info

Behavioral variant FTD (bvFTD)	Progressive changes in personality, social conduct, and executive function, with early behavioral disinhibition, apathy, loss of empathy, and compulsive/ritualistic behaviors
Associated Genes	ACHE, AD, AKT, AMYLOID, APOE, APP, BDNF, C9orf72
KG Connections	792 knowledge graph edges
Databases	OMIM Orphanet ClinicalTrials PubMed

Wiki Pages (21)

Knowledge base pages for this entity

Canonical Page

Pathway Diagram

graph TD
    FTD["FTD"] -->|"interacts"| FUS["FUS"]
    FTD["FTD"] -->|"interacts"| LC3["LC3"]
    FTD["FTD"] -->|"interacts"| OPTN["OPTN"]
    FTD["FTD"] -->|"interacts"| P62["P62"]
    FTD["FTD"] -->|"interacts"| SQSTM1["SQSTM1"]
    FTD["FTD"] -->|"interacts"| STING["STING"]
    ALS["ALS"] -->|"activates"| FTD["FTD"]
    NEURODEGENERATION["NEURODEGENERATION"] -->|"associated"| FTD["FTD"]
    C9ORF72["C9ORF72"] -->|"causes"| FTD["FTD"]
    AUTOPHAGY["AUTOPHAGY"] -->|"activates"| FTD["FTD"]
    style FTD fill:#ef5350,stroke:#4fc3f7,stroke-width:2px,color:#e0e0e0

Outgoing (450)

Target	Relation	Type	Str
UBQLN2	associated_with	gene	0.80
SIRT1	targets	gene	0.70
HTT	interacts_with	gene	0.70
MAPT	interacts_with	gene	0.70
NRF2	interacts_with	gene	0.70
GFAP	activates	gene	0.70
GBA	interacts_with	gene	0.70
MACROPHAGE	regulates	cell_type	0.70
NEURONS	degrades	cell_type	0.70
VCP	associated_with	gene	0.70
RIPK1	activates	gene	0.70
RAGE	interacts_with	gene	0.70
GRN	protects_against	gene	0.70
TREM2	markers	gene	0.70
MAPT	markers	gene	0.70
STING	markers	gene	0.70
NEURONS	interacts_with	cell_type	0.70
VCP	expresses	gene	0.70
PSEN1	interacts_with	gene	0.70
TREM2	activates	gene	0.70
LRRK2	interacts_with	gene	0.70
NEURONS	expressed_in	cell_type	0.70
VCP	stabilizes	gene	0.70
PROGRESSIVE SUPRANUCLEAR PALSY	regulates	disease	0.70
GRN	regulates	gene	0.70
LEWY BODY DEMENTIA	regulates	disease	0.70
RAGE	causes	gene	0.70
TFEB	regulates	gene	0.70
LEWY BODY DEMENTIA	markers	disease	0.70
TARDBP	associated_with	gene	0.70
FUS	associated_with	gene	0.70
TAU	associated_with	gene	0.65
PARKINSON'S DISEASE	associated_with	disease	0.65
NEURON	expressed_in	cell_type	0.65
NEURODEGENERATION	expressed_in	disease	0.65
MOTOR NEURON	activates	cell_type	0.65
NEURON	activates	cell_type	0.65
NEURONS	activates	cell_type	0.65
STING	causes	gene	0.65
TAU	interacts_with	gene	0.65
OPTN	transports	gene	0.65
SQSTM1	transports	gene	0.65
TAU	causes	gene	0.65
NEURON	phosphorylates	cell_type	0.65
NEURONS	phosphorylates	cell_type	0.65
TAU	phosphorylates	gene	0.65
PARKIN	impairs	gene	0.65
PARKINSON	impairs	disease	0.65
NEURON	regulates	cell_type	0.65
RAPAMYCIN	interacts_with	drug	0.65

Incoming (711)

Source	Relation	Type	Str
ALS	associated_with	disease	1.00
ALS	activates	disease	1.00
ALS	interacts_with	disease	1.00
PARKINSON'S DISEASE	associated_with	disease	1.00
TARDBP	associated_with	gene	1.00
ALZHEIMER'S DISEASE	associated_with	disease	1.00
ALS	causes	disease	0.98
ALS	regulates	disease	0.98
TAU	associated_with	protein	0.98
C9ORF72	associated_with	gene	0.95
VCP	associated_with	gene	0.95
TARDBP	causes	protein	0.95
FUS	associated_with	protein	0.95
Tau 3R/4R Ratio	biomarker_for	biomarker	0.93
TDP-43	causes	protein	0.90
RNA Splicing	associated_with	phenotype	0.90
C9orf72 HRE	risk_factor_for	gene	0.90
Cryptic Hdgfl2	biomarker_for	biomarker	0.90
TDP-43	associated_with	protein	0.90
Rbp Dysfunction	associated_with	phenotype	0.90
C9orf72 expansions	risk_factor_for	gene	0.90
TBK1	risk_factor_for	gene	0.90
Rbp Dysfunction	contributes_to	mechanism	0.90
VCP mutations	increases_risk	gene	0.90
Ggggcc Repeat Expansion	risk_factor_for	biomarker	0.90
TDP-43	associated_with	protein	0.90
FUS	causes	gene	0.90
GGGGCC Repeat Expansion	associated_with	biomarker	0.90
STING	associated_with	protein	0.90
Als	associated_with	disease	0.90
Ftld	associated_with	disease	0.90
C9ORF72	causes	gene	0.87
TARDBP	cross_disease_mechanism_in	gene_or_pathway	0.86
G3BP1	implicated_in	entity	0.85
C9ORF72	cross_disease_mechanism_in	gene_or_pathway	0.83
MAPT	cross_disease_mechanism_in	gene_or_pathway	0.82
MAPT	associated_with	gene	0.82
P53	associated_with	gene	0.80
vesicle trafficking	associated_with	pathway	0.80
DIPEPTIDE REPEAT PROTEINS (DPRS)	causes	compound	0.80
C9ORF72 REPEAT RNA	causes	compound	0.80
C9ORF72	associated_with	gene	0.80
stress_granule_formation	contributes_to	pathway	0.80
AMYLOID	associated_with	protein	0.74
TIA1	cross_disease_mechanism_in	gene_or_pathway	0.74
SOD1	associated_with	gene	0.74
TBK1	cross_disease_mechanism_in	gene_or_pathway	0.73
TDP43	associated_with	protein	0.72
GGGGCC_repeat	causes	genetic_variant	0.72
VESICLE_TRAFFICKING	associated_with	pathway	0.72

Targeting Hypotheses (12)

Hypotheses where this entity is a therapeutic target

Hypothesis	Score	Disease	Analysis
TDP-43 RNA-proteostasis failure across ALS, FTD, and AD/LATE	0.828	multi	Cross-disease neurodegeneration mechanis
Microglial AIM2 Inflammasome as the Primary Driver of TDP-43	0.824	neurodegeneration	What are the mechanisms by which gut mic
C9ORF72 autophagy-lysosome collapse across ALS and FTD	0.816	multi	Cross-disease neurodegeneration mechanis
MAPT tau seeding and release across AD, FTD, and PD-spectrum	0.812	multi	Cross-disease neurodegeneration mechanis
Stress-granule RNA-binding protein phase transition across A	0.780	multi	Cross-disease neurodegeneration mechanis

TBK1-OPTN-p62 selective autophagy failure across ALS, FTD, a	0.776	multi	Cross-disease neurodegeneration mechanis
GRN/progranulin lysosomal insufficiency across FTD, ALS-spec	0.756	multi	Cross-disease neurodegeneration mechanis
C9orf72 ASO Treatment Reverses TDP-43 Pathology in ALS/FTD	0.720	neurodegeneration	Test Hypothesis Fixtures
Astrocyte-Neuron Metabolic Coupling Failure Precedes Neurode	0.690	neurodegeneration	Gap 006 analysis (archived stub)
FUS Phase Separation Dominance in FTD-TDP: Aberrant Condensa	0.683	Frontotemporal dementia	-
Stathmin-2 Splice Switching to Prevent Axonal Degeneration A	0.664	neurodegeneration	RNA binding protein dysregulation across
Nuclear TDP-43 Depletion Drives Synaptic Splicing Dysregulat	0.620	neurodegeneration	Gap 006 analysis (archived stub)

Mentioning Analyses (13)

Scientific analyses that reference this entity

Cross-disease neurodegeneration mechanism synthesis

neurodegeneration | 2026-04-28 | 17 hypotheses Top: 0.828

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

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

test debate

neurodegeneration | 2026-04-15 | 0 hypotheses

How does FUS loss-of-function in TAZ regulation contribute to ALS/FTD pathogenes

neurodegeneration | 2026-04-14 | 1 hypotheses Top: 0.720

What molecular mechanism causes VCP mutations to trigger aberrant HIF-1α activat

neurodegeneration | 2026-04-13 | 2 hypotheses Top: 0.793

Experiments (6)

Experimental studies targeting or related to this entity

Experiment	Type	Disease	Score	Feasibility	Model	Status	Est. Cost
Mechanism: C9orf72 Hexanucleotide Repeat Expansion in ALS/FTD	validation	ALS	0.400	0.50	human	proposed	$2,730,000
Progranulin Replacement Therapy for FTD — Vector Development and Valid	clinical	ALS	0.400	0.50	human	proposed	$5,460,000
FTD Microglia Role: Protective vs Destructive Mechanism Study	validation	Neuroinflammation	0.400	0.50	human	proposed	$2,960,000
Frontal and Temporal Lobe Selective Vulnerability in FTD — Mechanisms	validation	Neurodegeneration	0.400	0.50	human	proposed	$3,000,000
C9orf72 Phenotype Divergence: ALS vs FTD Mechanism Study	clinical	ALS	0.400	0.50	human	proposed	$6,550,000
Autophagy Enhancement Drug Screening for Neurodegeneration	clinical	Alzheimer's Disease	0.400	0.50	human	proposed	$6,550,000

Related Papers (20)

Scientific publications cited in analyses involving this entity

Title & PMID	Authors	Journal	Year	Citations
Small molecule-driven NLRP3 inflammation inhibition via interplay between ubiqui [PMID:30966861]	["Han X", "Sun S", "Sun Y", "Song Q", "Z	Autophagy	2020	1
The TREM2-APOE Pathway Drives the Transcriptional Phenotype of Dysfunctional Mic [PMID:28930663]	Krasemann S, Madore C, Cialic R, Baufeld	Immunity	2017	1
Inhibition of autophagy in microglia and macrophages exacerbates innate immune r [PMID:36652438]	Hegdekar N, Sarkar C, Bustos S, Ritzel R	Autophagy	2023	0
Inflammasome assembly in neurodegenerative diseases. [PMID:37633753]	Singh J, Habean ML, Panicker N	Trends in neurosciences	2023	0
NLRP3/caspase-1/GSDMD-mediated pyroptosis exerts a crucial role in astrocyte pat [PMID:34877938]	Li S, Sun Y, Song M, Song Y, Fang Y, Zha	JCI insight	2021	0
PINK1/PARKIN signalling in neurodegeneration and neuroinflammation. [PMID:33168089]	Quinn PMJ, Moreira PI, Ambrósio AF, Alve	Acta neuropathologica communic	2020	0
Inflammasome inhibition prevents α-synuclein pathology and dopaminergic neurodeg [PMID:30381407]	Gordon R, Albornoz EA, Christie DC, Lang	Science translational medicine	2018	0
LRRK2 Promotes Tau Accumulation, Aggregation and Release. [PMID:26014385]	Unknown	Molecular neurobiology	2017	0
TIA1 Mutations in Amyotrophic Lateral Sclerosis and Frontotemporal Dementia Prom [PMID:28817800]	["Mackenzie Ian R", "Nicholson Alexandra	Neuron	2017	0
Haploinsufficiency of TBK1 causes familial ALS and fronto-temporal dementia. [PMID:25803835]	Unknown	Nature neuroscience	2015	0
The roles of PINK1, parkin, and mitochondrial fidelity in Parkinson's disease. [PMID:25611507]	["Pickrell Alicia M", "Youle Richard J"]	Neuron	2015	0
Mutations in prion-like domains in hnRNPA2B1 and hnRNPA1 cause multisystem prote [PMID:23455423]	Unknown	Nature	2013	0
A hexanucleotide repeat expansion in C9ORF72 is the cause of chromosome 9p21-lin [PMID:21944779]	Unknown	Neuron	2011	0
Expanded GGGGCC hexanucleotide repeat in noncoding region of C9ORF72 causes chro [PMID:21944778]	["DeJesus-Hernandez Mariely", "Mackenzie	Neuron	2011	0
Etiology and pathophysiology of frontotemporal dementia, Parkinson disease and A [PMID:18322368]	Unknown	Neuro-degenerative diseases	2008	0
TDP-43 immunoreactivity in hippocampal sclerosis and Alzheimer's disease. [PMID:17469117]	Unknown	Annals of neurology	2007	0
Mutations in progranulin cause tau-negative frontotemporal dementia linked to ch [PMID:16862116]	Unknown	Nature	2006	0
Null mutations in progranulin cause ubiquitin-positive frontotemporal dementia l [PMID:16862115]	Unknown	Nature	2006	0
Ubiquitinated TDP-43 in frontotemporal lobar degeneration and amyotrophic latera [PMID:17023659]	Unknown	Science (New York, N.Y.)	2006	0
The role of tau (MAPT) in frontotemporal dementia and related tauopathies. [PMID:15365985]	Unknown	Human mutation	2005	0

Debates (20)

Multi-agent debates referencing this entity

Which AD, PD, ALS, and FTD mechanisms recur across disease boundaries and yield

active · Rounds: 4 · Score: 0.72 · 2026-04-28

Debate: TREM2 Microglial Activation Rescues Amyloid Clearance in AD

closed · Rounds: 4 · Score: 0.75 · 2026-04-27

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

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

Hypothesis debate: C9orf72 ASO Treatment Reverses TDP-43 Pathology in ALS/FTD

closed · Rounds: 4 · Score: 0.58 · 2026-04-27

Hypothesis debate: Stathmin-2 Splice Switching to Prevent Axonal Degeneration Ac

closed · Rounds: 4 · Score: 0.49 · 2026-04-27

Investigate how microglial senescence drives ALS progression through inflammatio

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

Hypotheses created for system testing (hyp_test_* prefix)

closed · Rounds: 4 · Score: 0.77 · 2026-04-26

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

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

Analysis for knowledge gap 006 in the neurodegeneration domain.

closed · Rounds: 4 · Score: 0.79 · 2026-04-22

The study shows TRIM21 and autophagy receptors can eliminate both physiological

closed · Rounds: 4 · Score: 0.75 · 2026-04-22

Related Research

Hypotheses and analyses mentioning FTD in their description or question text

TBK1-OPTN-p62 selective autophagy failure across ALS, FTD, and PD-like proteotox

Score: 0.776 · multi · 2026-04-28

Shared mechanism across ALS, FTD, PD: TBK1 coordinates selective autophagy adaptors and innate immune tone. TBK1 haploin

GRN/progranulin lysosomal insufficiency across FTD, ALS-spectrum stress, and AD

Score: 0.756 · multi · 2026-04-28

Shared mechanism across FTD, ALS, AD: Progranulin insufficiency causes tau-negative, ubiquitin-positive FTD and weakens

C9orf72 ASO Treatment Reverses TDP-43 Pathology in ALS/FTD

Score: 0.720 · neurodegeneration · 2026-04-26

Antisense oligonucleotides targeting C9orf72 hexanucleotide repeat expansion reduce toxic DPR proteins and RNA foci, res

Astrocyte-Neuron Metabolic Coupling Failure Precedes Neurodegeneration in FTD-GR

Score: 0.690 · neurodegeneration · 2026-04-22

**Molecular Mechanism and Rationale** The pathogenesis of frontotemporal dementia with GRN mutations (FTD-GRN) involves

Stathmin-2 Splice Switching to Prevent Axonal Degeneration Across the ALS-FTD-AD

Score: 0.664 · neurodegeneration · 2026-04-13

**Molecular Mechanism and Rationale** The stathmin-2 splice switching therapeutic approach targets a fundamental pathom

Nuclear TDP-43 Depletion Drives Synaptic Splicing Dysregulation in ALS-FTD

Score: 0.620 · neurodegeneration · 2026-04-22

## Mechanistic Overview Nuclear TDP-43 Depletion Drives Synaptic Splicing Dysregulation in ALS-FTD starts from the claim

FTD

Understanding Entity Pages

Wiki Pages (21)

Frontotemporal Dementia (FTD)

Frontotemporal Dementia (FTD) Mechanistic Pathway

Epigenetic Dysregulation Comparison -- AD/PD/ALS/FTD/HD

Lipid Metabolism Dysfunction Comparison — AD/PD/ALS/FTD/HD

Autophagy-Lysosomal Impairment Comparison — AD/PD/ALS/FTD/HD

Neuroinflammation Across AD, PD, ALS, FTD, and HD

ALS-FTD Spectrum

Autophagy Failure Comparison -- AD/PD/ALS/FTD/HD

FTD Tau Subtypes Comparison: 3R vs 4R Tauopathies

FTD-ALS Spectrum

C9orf72→RNA/Dipeptide Repeat Pathology→ALS/FTD — Causal Chain

Mechanism: Progranulin Loss and TDP-43 Pathology in FTD

Neuroinflammation Comparison — AD/PD/ALS/FTD/HD

FUS Gene-Mechanism-Therapy Causal Chain — ALS/FTD

GRN Progranulin FTD Causal Chain

Neurovascular Coupling Disease Comparison — AD/PD/ALS/FTD/HD

Mitochondrial Dysfunction in ALS-FTD Spectrum

VCP→TDP-43→ALS/FTD Causal Chain

AD-FTD Tau-TDP-43 Overlap: Mechanism Comparison

Behavioral Variant FTD: Network and Molecular Mechanisms

Interoceptive Brain Dynamics in bvFTD

Pathway Diagram

Outgoing (450)

Incoming (711)

Targeting Hypotheses (12)

Mentioning Analyses (13)

Cross-disease neurodegeneration mechanism synthesis

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

test debate

How does FUS loss-of-function in TAZ regulation contribute to ALS/FTD pathogenes

What molecular mechanism causes VCP mutations to trigger aberrant HIF-1α activat

RNA binding protein dysregulation across ALS FTD AD

What determines the temporal transition from protective to pathological stress g

How does TRIM21-mediated K63 ubiquitination of G3BP1 mechanistically inhibit liq

How do pathological stress granules in neurodegeneration escape TRIM21/autophagy

Gap 006 analysis (archived stub)

RNA binding protein dysregulation across ALS FTD and AD

TDP-43 phase separation therapeutics for ALS-FTD

Test Hypothesis Fixtures

Experiments (6)

Related Papers (20)

Debates (20)

Which AD, PD, ALS, and FTD mechanisms recur across disease boundaries and yield

Debate: TREM2 Microglial Activation Rescues Amyloid Clearance in AD

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

Hypothesis debate: C9orf72 ASO Treatment Reverses TDP-43 Pathology in ALS/FTD

Hypothesis debate: Stathmin-2 Splice Switching to Prevent Axonal Degeneration Ac

Investigate how microglial senescence drives ALS progression through inflammatio

Hypotheses created for system testing (hyp_test_* prefix)

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

Analysis for knowledge gap 006 in the neurodegeneration domain.

The study shows TRIM21 and autophagy receptors can eliminate both physiological

Related Research

TBK1-OPTN-p62 selective autophagy failure across ALS, FTD, and PD-like proteotox

GRN/progranulin lysosomal insufficiency across FTD, ALS-spectrum stress, and AD

C9orf72 ASO Treatment Reverses TDP-43 Pathology in ALS/FTD

Astrocyte-Neuron Metabolic Coupling Failure Precedes Neurodegeneration in FTD-GR

Stathmin-2 Splice Switching to Prevent Axonal Degeneration Across the ALS-FTD-AD

Nuclear TDP-43 Depletion Drives Synaptic Splicing Dysregulation in ALS-FTD