Mutant TDP-43, but not mutant Fus, mice displayed a pre-symptomatic deficiency in endosome transport, suggesting that reduced neurotrophin signaling may contribute to mutant TDP-43-mediated neuropathology and that general defects in axonal transport are specific to a subset of ALS-linked genes in an in vivo mammalian setting. This evidence concerns the gene BDNF and amyotrophic lateral sclerosis.