In this study, to define the pathomechanisms of sporadic ALS/FTD and to investigate the contribution of aging to the formation of such phenotypes, we generated Tg mice expressing wild-type TDP-43 under the control of the mouse prion promoter and defined the pathology, behaviour, and genes affected by the dysregulation of TDP-43 during aging. Here, TARDBP is linked to frontotemporal dementia.