TARDBP and amyotrophic lateral sclerosis: This conceptualization is supported by the observation that the neuropathological hallmark of the vast majority of ALS cases, regardless of the presence or absence of ALS-FTSD, is the presence of pathological cytoplasmic TDP-43 inclusions reflective of disruption in the metabolism of TDP-43 and thus sharing a feature in common with a subset of FTD patients (35, 36).