TARDBP and Alzheimer disease: According to the traditional viewpoint, the aggregation of one or two specific proteins is regarded as a characteristic of a disease, and severing is the biomarker [2,3,4,5]; for example, as seen in amyloid β (Aβ) and the Tau protein (Tau) for AD [7,8,9], α-synuclein (α-Syn) for PD [10,11,12], huntingtin (Htt) for HD [13,14] and transactive response DNA-binding protein 43 (TDP-43) for ALS and frontotemporal lobar degeneration (FTLD) [15,16].