This occurs notably in the upper and lower motor neurons in the motor cortex and spinal cord for ALS, and von Economo neurons and fork cells in the frontoinsular and anterior cingulate cortices in most cases of frontotemporal lobar degeneration with TDP-43 pathology (FTLD-TDP), the pathological entity which causes approximately half of all FTD [78–81] (Fig. 2). Here, TARDBP is linked to amyotrophic lateral sclerosis.