TDP-43 proteinopathy

E561103

neurodegenerative disease proteinopathy

TDP-43 proteinopathy is a neurodegenerative condition characterized by abnormal aggregation and mislocalization of the TDP-43 protein, commonly implicated in disorders such as amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD).

Try in SPARQL Jump to: Surface forms Disambiguation Statements Elicitation Referenced by

All labels observed (3)

Label	Occurrences
FTLD-TDP	1
TDP-43 proteinopathy canonical	1
limbic-predominant age-related TDP-43 encephalopathy	1

How this entity was disambiguated

This entity first appeared as the object of triple T6004835 — resolving that mention is where its identity was fixed. The disambiguator weighed these candidate entities and picked the highlighted one (or “None”, minting a new entity). This is how homonymy is resolved: the same surface form can point to different entities.

NED1 Entity disambiguation (via context triple) gpt-5-mini-2025-08-07

Target entity: TDP-43 proteinopathy
Context triple: [C9orf72, associatedWithPathology, TDP-43 proteinopathy]

A. C9orf72
C9orf72 is a human gene whose hexanucleotide repeat expansions are the most common known genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD).
B. survival motor neuron protein
Survival motor neuron protein is an essential cellular protein required for the maintenance and function of motor neurons, whose deficiency leads to spinal muscular atrophy.
C. SOD1
SOD1 is a gene encoding the antioxidant enzyme superoxide dismutase 1, whose mutations are a major known cause of familial amyotrophic lateral sclerosis (ALS).
D. ALS
ALS (amyotrophic lateral sclerosis) is a progressive neurodegenerative disease that affects nerve cells in the brain and spinal cord, leading to muscle weakness, paralysis, and ultimately respiratory failure.
E. ALS
ALS is the abbreviation for the Army Legal Services Branch, the specialist legal branch of the British Army responsible for providing legal support and advice.
F. None of above. chosen
G. Unsure - the case is ambiguous/there is not enough information to decide.

NED2 Entity disambiguation (via description) gpt-5-mini-2025-08-07

Target entity: TDP-43 proteinopathy
Target entity description: TDP-43 proteinopathy is a neurodegenerative condition characterized by abnormal aggregation and mislocalization of the TDP-43 protein, commonly implicated in disorders such as amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD).

A. C9orf72
C9orf72 is a human gene whose hexanucleotide repeat expansions are the most common known genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD).
B. survival motor neuron protein
Survival motor neuron protein is an essential cellular protein required for the maintenance and function of motor neurons, whose deficiency leads to spinal muscular atrophy.
C. SOD1
SOD1 is a gene encoding the antioxidant enzyme superoxide dismutase 1, whose mutations are a major known cause of familial amyotrophic lateral sclerosis (ALS).
D. ALS
ALS (amyotrophic lateral sclerosis) is a progressive neurodegenerative disease that affects nerve cells in the brain and spinal cord, leading to muscle weakness, paralysis, and ultimately respiratory failure.
E. ALS
ALS is the abbreviation for the Army Legal Services Branch, the specialist legal branch of the British Army responsible for providing legal support and advice.
F. None of above. chosen

Statements (55)

Predicate	Object
instanceOf	neurodegenerative disease ⓘ proteinopathy ⓘ
abbreviationOfAssociatedProtein	TDP-43 ⓘ linked to: TARDBP
affectsBrainRegion	frontal cortex ⓘ hippocampus ⓘ spinal cord anterior horn ⓘ temporal cortex ⓘ
affectsCellType	cortical neurons ⓘ hippocampal neurons ⓘ motor neurons ⓘ
associatedWithDisease	ALS with frontotemporal dementia ⓘ Alzheimer’s disease ⓘ linked to: Alzheimer's disease Guam parkinsonism-dementia complex ⓘ HIV-associated neurocognitive disorders ⓘ Perry syndrome ⓘ amyotrophic lateral sclerosis ⓘ chronic traumatic encephalopathy ⓘ corticobasal degeneration with TDP-43 pathology ⓘ frontotemporal dementia ⓘ linked to: Pick’s disease frontotemporal lobar degeneration ⓘ inclusion body myopathy with Paget disease and frontotemporal dementia ⓘ limbic-predominant age-related TDP-43 encephalopathy ⓘ linked to: TDP-43 proteinopathy
characterizedBy	C-terminal fragments of TDP-43 ⓘ TDP-43-positive cytoplasmic inclusions ⓘ abnormal aggregation of TDP-43 ⓘ abnormal phosphorylation of TDP-43 ⓘ mislocalization of TDP-43 from nucleus to cytoplasm ⓘ nuclear clearance of TDP-43 ⓘ ubiquitination of TDP-43 aggregates ⓘ
hasAssociatedProtein	TAR DNA-binding protein 43 ⓘ linked to: TARDBP
hasBiomarker	TDP-43 fragments in brain tissue ⓘ TDP-43-positive inclusions on neuropathology ⓘ phosphorylated TDP-43 immunoreactivity ⓘ
hasConsequence	behavioral changes ⓘ cognitive impairment ⓘ gliosis ⓘ motor dysfunction ⓘ neuron loss ⓘ
hasPathologyType	ALS-TDP ⓘ linked to: ALS FTLD-TDP ⓘ linked to: TDP-43 proteinopathy
hasRiskFactor	C9orf72 hexanucleotide repeat expansion ⓘ linked to: C9orf72 GRN gene mutations ⓘ TARDBP gene mutations ⓘ VCP gene mutations ⓘ
involvesProcess	RNA metabolism dysregulation ⓘ aberrant stress granule dynamics ⓘ gain of toxic cytoplasmic TDP-43 function ⓘ impaired RNA splicing ⓘ impaired autophagy ⓘ impaired proteostasis ⓘ impaired ubiquitin-proteasome system ⓘ loss of nuclear TDP-43 function ⓘ protein misfolding ⓘ
studiedInModel	cell culture models with TDP-43 overexpression ⓘ transgenic mouse models expressing mutant TDP-43 ⓘ

How these facts were elicited

Referenced by (3)

Full triples — surface form annotated when it differs from this entity's canonical label.

C9orf72 → associatedWithPathology → TDP-43 proteinopathy ⓘ

TDP-43 proteinopathy → associatedWithDisease → limbic-predominant age-related TDP-43 encephalopathy ⓘ

linked to: TDP-43 proteinopathy

TDP-43 proteinopathy → hasPathologyType → FTLD-TDP ⓘ