However, more extensive biochemical and biophysical studies are needed to show the presence of distinct pathogenic TDP-43 strains in FTLD-TDP and ALS CNS, possibly related to the presence of different TDP-43 conformers (i.e., strains) with a specific tropism for selected brain areas and characterized by a different seeding ability, resulting, ultimately, in the extreme clinical heterogeneity observed in FTLD-TDP and ALS patients. This evidence concerns the gene TARDBP and amyotrophic lateral sclerosis.