TARDBP and proteostasis deficiencies: TDP-43 was recently established as the major pathological protein in FTD with ubiquitin-positive and tau-negative inclusions, with or without motor neuron disease/ALS, and in sporadic ALS, establishing the concept of a spectrum of "TDP-43 proteinopathies." This protein is also widely present in CTE and in some cases the TDP-43 proteinopathy involves the spinal cord and may be associated with ALS (McKee et al. 2010).