Blinded quantification of ALYREF intensity revealed that upregulation of ALYREF was stronger in C9+ ALS cases, which have both TDP-43 pathology and the G4C2 repeat expansion present in C9orf72 [1, 13, 38, 42], compared to C9- ALS cases, which have only TDP-43 pathology [14, 32] (Fig. 5c). This evidence concerns the gene C9 and amyotrophic lateral sclerosis.