SOD1 mutation is assosiated with accumulation of neurofilaments in amyotrophic lateral scelaries

Abstract

Mutations in the Cu/Zn superoxide dismutase (SODl) gene are found in 15 to 20% of patients with familial amyotrophic lateral sclerosis (FALS). Increased levels of neurofilament subunits in transgenic mouse models of ALS also suggests a key role for these proteins in the pathogenesis of the disease. We report the coexistence of an Ile¹¹³ → Thr substitution in exon 4 of the SOD1 gene and marked neurofilamentous pathology in the same FALS patient. These observations suggest that two mechanisms, SOD 1‐induced toxicity and neurofilament disruption, are acting together.