The mid-1980s saw the emergence of a more subtle dysexecutive neuropsychological syndrome,31 followed by positron emission tomography studies providing further evidence of wide cerebral involvement in ALS.32, 33 The finding of a shared neuropathological signature of cytoplasmic ubiquitinated inclusions of the protein TDP-43 in ALS and frontotemporal dementia (FTD)34 is probably the most important clinicomolecular discovery in ALS research to date. Here, TARDBP is linked to amyotrophic lateral sclerosis.