disease 3,586 words KG: ent-dise-d0429769 2026-03-24
kind:diseasesection:diseasesstate:publishedevidence:strong
Contents

ALS-FTD Spectrum

Disease Info
GRN (Progranulin)Loss-of-function mutations cause progranulin-deficient FTD (FTD-TDP type A), and some patients develop motor neuron features 10.
MAPT (Tau)Mutations in the microtubule-associated protein tau gene cause FTD-Tau, but motor neuron disease is uncommon 11.
ALSIN gene (ALS2)Juvenile-onset ALS with FTD features, caused by recessive ALSIN mutations 12.
SOD1 (Superoxide dismutase 1)First gene linked to familial ALS, but does not typically cause FTD 13.
Type A (Motor)Numerous small neurites and neuronal cytoplasmic inclusions, associated with GRN mutations and ALS
Type B (Bulbar)Moderate numbers of neuronal cytoplasmic inclusions without neurites, common in ALS-FTD with C9orf72
Type C (Cortical)Long dystrophic neurites, associated with semantic variant FTD
Type D (Hippocampal)Hippocampal neuronal inclusions, associated with VCP mutations 15
Dipeptide repeat proteinsImmunoreactive inclusions for poly-GA, poly-GR, poly-PR, and other DPRs, particularly in the frontal cortex and hippocampus 16.
Neuronal nucleolar stressThe C9orf72 repeat expansion causes nucleolar dysfunction, with TDP-43 translocating from nucleus to cytoplasm 17.
DatabasesOMIMOrphanetClinicalTrialsPubMed

Knowledge Graph

Related Hypotheses (20)

Microglial AIM2 Inflammasome as the Primary Driver of TDP-43
Score: 0.60
Multiplexed Base Editing for Simultaneous Neuroprotective Ge
Score: 0.53
Acid-Degradable LNP-Mediated Prenatal CRISPR Intervention fo
Score: 0.47
Cryptic Exon Silencing Restoration
Score: 0.46
Cross-Seeding Prevention Strategy
Score: 0.45

Related Analyses (20)

CRISPR-based therapeutic approaches for neurodegenerative di
neurodegeneration · completed
How do pathological stress granules in neurodegeneration esc
neurodegeneration · failed
What determines the specificity of TDP-43-induced mitochondr
neurodegeneration · failed
How does chronic cGAS/STING activation downstream of TDP-43
neuroinflammation · failed
What mechanisms drive TDP-43 pathology specifically in Alzhe
neurodegeneration · failed

Related Experiments (30)

cGAS/STING pathway activation by TDP-43-released mtDNA
exploratory · proposed · Score: 0.95
TDP-43 mutant mouse model cGAS/STING pathway analysis
validation · proposed · Score: 0.90
TDP-43 mitochondrial invasion and mtDNA release in iPSC moto
exploratory · proposed · Score: 0.90
cGAMP biomarker analysis in ALS patient spinal cord samples
clinical · proposed · Score: 0.85
cGAMP biomarker analysis in ALS patient spinal cord samples
exploratory · proposed · Score: 0.80