Accumulation of neurofilaments and SOD1-immunoreactive products in a patient with familial amyotrophic lateral sclerosis with I113T SOD1 mutation

Objective: To report neuropathologic features of argyrophilic inclusions in the anterior horn cells, motor cortex Betz cells, and neurons of the medul lary reticular formation, spinal posterior horn, and Clarke column in a Jap anese case of familial amyotrophic lateral sclerosis with 1113T substitutio n in exon 4 of the copper-zinc superoxide dismutase (SOD1) gene. Methods and Results: These inclusions were stained pale pink on the hematox ylin-eosin stain and dark on the Bielschowsky stain. They were positive for antibodies to phosphorylated neurofilaments, ubiquitin, and SOD1. On elect ron microscopy, they consisted of abundant intermediate filaments of 10 to 20 nm in diameter with disordered array indicating neurofilaments. Conclusion: These findings suggest that the 1113T mutation induces accumula tion of neurofilaments and SOD1 in the central nervous system neurons.