In the current study, we sought to utilize mouse models of Aβ amyloidosis, tauopathy, α-synucleinopathy, and a polyglutamine disorder (HD) to determine if any aspect of TDP-43 pathology can be driven in vivo by an independent primary pathological aggregate (e.g., tau) caused by a defined genetic event (e.g., mutant tau). The gene discussed is TARDBP; the disease is Huntington disease.