Here, we report proof-of-concept that a novel SOD1 seed amplification assay can detect misfolded SOD1 in patient spinal cords and motor cortices with familial (SOD1, C9ORF72) or sporadic cases of ALS (i.e., ≥ 90% of all ALS cases), which may translate to a potential biomarker for this neuromuscular disease. The gene discussed is SOD1; the disease is amyotrophic lateral sclerosis.