To test whether the spreading of pathological TDP-43 via pyramidal tract can induce ALS-like phenotypes, we first generated a Thy1-e (IRES-TARDBP) 1 mouse line, specifically expressing hTDP-43 in nervous system, and evaluated the pathological phenotype of this mouse model on the behavior, molecular, and cellular levels. Here, THY1 is linked to amyotrophic lateral sclerosis.