TARDBP and proteostasis deficiencies: A neuropathological feature of TDP-43 proteinopathies is the mislocalization of TDP-43, from its predominantly nuclear location into the cytosol, where it accumulates [29] To determine whether there is mislocalization of TDP-43 and TDP-35 in the brains of the 3×Tg-AD mice, we extracted nuclear and cytosolic proteins from the brains of 2-, 6-, 12-month-old 3×Tg-AD and NonTg mice (n = 6/genotype/time-point).