An autopsy case of SOD1 -related ALS with TDP-43 positive inclusions

Abstract

Approximately 20% of familial amyotrophic lateral sclerosis (FALS) cases are linked to mutations in the antioxidant enzyme, Cu/Zn superoxide dismutase (SOD1) . Controversy exists as to whether SOD1 -related FALS and sporadic ALS (SALS) share common mechanistic pathways, since very few SOD1 -related FALS cases exhibit cytoplasmic inclusions composed of 43-kDa TAR DNA-binding protein (TDP-43), a pathologic hallmark of SALS and SOD1 -unrelated FALS.1,2,e1,e2 We describe prominent TDP-43 pathology in the spinal cord of a patient with SOD1 -related ALS with SOD1 I112T mutation, a relatively uncommon variant form leading to rapid disease progression.3 ### Case report. A 41-year-old man with no familial history of neurodegenerative disorder noted progressive weakness in his left leg. Four months after onset, a neurologic examination detected muscle weakness in the left lower extremity and fasciculation in all the extremities. Tendon reflexes were decreased and Babinski sign was negative bilaterally; EMG revealed a neurogenic pattern in the left extremities. Dysarthria and dysphagia were not evident. He was diagnosed with ALS. Within a year, he became bedridden and died at the age of 43 because of respiratory failure. Genomic DNA was extracted from the autopsied samples with informed consent from his family. DNA analysis revealed a …