An autopsy case of familial amyotrophic lateral sclerosis with a TARDBP Q343R mutation

We describe a Japanese autopsy case of familial amyotrophic lateral sclerosis (FALS) with a TARDBP Q343R mutation. This male patient developed dysarthria at the age of 52 years, and bulbar symptoms progressed, with weakness and atrophy in the extremities. His mental status was normal, but he became bedridden, received artificial respiratory support at 54 years of age, and gradually acquired a locked‐in state and died at 58 years of age. Microscopically, marked diffuse myelin pallor was observed in the anterolateral columns of the spinal cord. The remaining anterior horn cells contained Bunina bodies and phosphorylation‐dependent transactivation response DNA‐binding protein of 43 kDa (pTDP‐43)‐positive neuronal cytoplasmic inclusions (NCIs). Glial cytoplasmic inclusions (GCIs) were also observed. The number of ubiquitin‐ and p62‐positive inclusions was markedly lower than that of pTDP‐43‐positive inclusions. NCIs and many fine dot‐like pTDP‐43‐positive granules in the neuropil were mainly seen in the temporal and motor cortices, and striatum. NCIs were rare in hippocampal granular cells. Immunoblotting of samples from the cerebral cortex using an anti‐pTDP‐43 antibody was slightly different from previous TDP‐43 pathological subtypes.