In this large-scale digital histopathological comparative study of WM and adjacent GM pathology in a clinically well-defined FTLD autopsy cohort, we find that greater WM pathology burden and WM degeneration is a consistent neuropathological feature of tauopathies compared to TDP-43 proteinopathies (Figs. 1, 2; Table 3). Here, TARDBP is linked to proteostasis deficiencies.