SOD1 MUTATION IS ASSOCIATED WITH ACCUMULATION OF NEUROFILAMENTS IN AMYOTROPHIC-LATERAL-SCLEROSIS

Mutations in the Cu/Zn superoxide dismutase (SOD1) gene are found in 1 5 to 20% of patients with familial amyotrophic lateral sclerosis (FALS ). Increased levels of neurofilament subunits in transgenic mouse mode ls of ALS also suggests a key role for these proteins in the pathogene sis of the disease. We report the coexistence of an Ile(113) --> Thr s ubstitution in exon 4 of the SOD1 gene and marked neurofilamentous pat hology in the same FALS patient. These observations suggest that two m echanisms, SOD1-induced toxicity and neurofilament disruption, are act ing together.