In prior published papers that have studied the spectrum of TDP-43 pathologies in aged brains (often with comorbid AD pathology), the severity of TDP-43 proteinopathy has been mostly graded according to stage-based classification systems where the presence of any TDP-43 pathology in a given region defines a particular stage [15, 17, 27, 29, 44]. Here, TARDBP is linked to proteostasis deficiencies.