TARDBP and prion disease: In analogy to prion diseases and other neurodegenerative diseases such as tau- and alpha-synucleinopathies, a popular hypothesis, supported by an increasing body of evidence, is that the heterogeneity is a reflection of biochemical differences in pathological TDP-43 species that propagate in a prion-like manner with different conformers being associated with distinct seeding/toxicity activities (i.e., TDP-43 strains) [5, 10, 11, 23, 29].