Furthermore, the SAP18 gene, with a mean average importance score of 5.33 for the ALS subtype categorization in frontal cortex samples (Additional file 1: Table S1), has been shown to be related to brain cell dysregulation and development of amyloid plaques in both Down Syndrome and Alzheimer’s disease (Sharma et al. 2021), while BAG1, also one of the topmost determinative genes for the ALS categorization, as a member of PQC system proteins, is highly expressed in muscle of TG-ALS mice (Cicardi et al. 2018). This evidence concerns the gene BAG1 and Down syndrome.