TARDBP and frontotemporal dementia: Although TAR DNA-binding protein 43 (TDP-43) aggregation was originally discovered in the brains of patients with frontotemporal lobar degeneration and amyotrophic lateral sclerosis (29), the TDP-43 pathology was identified in approximately 20 to 50% of individuals with AD (30), and this number increased to 75% when only high-stage AD cases were included (31), leading to the proposal of a disease entity known as limbic-predominant age-related TDP-43 encephalopathy (32).