A 12-person case study of CTE showed that 10 of these cases had widespread TAR DNA-binding protein 43 (TDP-43) pathology, with three of these individuals developing progressive ALS several years before death.52 Nuclear depletion and cytoplasmic aggregation of TDP-43 within motor neurons represent the hallmark pathology of ALS.53 However, it should be pointed out that the population of neurons affected by CTE is distinct from ALS. Here, TARDBP is linked to amyotrophic lateral sclerosis.