τ, TDP-43, and α-syn alone lead to specific neurodegenerative disorders that do not necessarily show multiple proteins aggregating in the respective disorders such as in FTLD-tau, FTLD-TDP, ALS, and PD, whereas AD appears to have at least a two-step pathogenesis with alterations in Aβ likely initiating the actual disease process, but with τ accumulation and spread through the brain being the essential step to cause disease symptoms. Here, TARDBP is linked to amyotrophic lateral sclerosis.