Skip to main content

Table 1 Phenotype-pathology correlations summary of FUS-linked human ALS/FTD

From: Pathogenesis of FUS-associated ALS and FTD: insights from rodent models

Disease Neuropathology Genetics Epidemiology Clinical features
ALS-FUS - Degeneration of both upper and lower motor neurons
- Significant neuronal loss within anterior horn of spinal cord
- Moderate neuronal loss of Betz cells within layer V of motor cortex and motor nuclei of brainstem
- Dystrophic neurites, astrogliosis, microglial activation
- TDP43-negative, FUS-positive neuronal cytoplasmic inclusions
FUS – over 50 mutations described, particularly missense variations within C-terminal Nuclear Localization Signal FUS mutations account for ~4 % fALS and ~1 % sALS - Progressive muscular atrophy
- Dysphagia
- Dysarthria
- Respiratory
- Rigid spasticity
- Death normally within 2–3 years from symptom onset
FTLD-FUS Atypical FTLD with Ub (aFTLD-U) - Widespread degeneration of frontal cortex and ventral temporal lobe
- Tau/TDP43-negative, FUS-positive neuronal or glial inclusions predominantly within hippocampus, amygdala, frontotemporal cortex and striatum
Rare cases of FUS variants in clinical FTLD (not confirmed pathologically) ~10 % FTLD cases display FUS pathology - Normally behavioural variant FTD
- Changes in personality and emotion
- Irrationality, compulsiveness, confusion, repetition, inappropriate behaviour
- Psychiatric symptoms, depression and anxiety common
- Memory, motor function and perception are relatively preserved until late disease stages
NIFID - Neuronal cytoplasmic inclusions containing abnormal intermediate filament accumulation
BIBD - Significant FUS-pathology plus subcortical basophilic inclusions on H&E staining
  1. ALS Amyotrophic Lateral Sclerosis (familial and sporadic), FTLD Frontotemporal Lobar Degeneration, NIFID Neuronal Intermediate Filament Inclusion Disease, BIBD Basophilic Inclusion Body Disease, FUS, Fused-insarcoma; H&E, Haematoxylin and eosin