In conclusion, this study shows that wild-type TDP-43 overexpression in the hypothalamus can lead to the development of neuropathological and molecular features similar to what have been reported for ALS/FTD including hypothalamic pathology with TDP-43 mislocalization and formation of TDP-43 nuclear and cytoplasmic inclusions (Fig. 8). This evidence concerns the gene TARDBP and amyotrophic lateral sclerosis.