Using hSOD1G93A and prpTDP-43A315T mouse models of ALS, which represent disease mechanisms that occur due to misfolded SOD1 toxicity and TDP-43 pathology, respectively, here, we reveal that CSMN based on the underlying cause of the disease display a distinct pattern of methylation and hydroxymethylation. The gene discussed is SOD1; the disease is amyotrophic lateral sclerosis.