In addition to hyperphosphorylated tau, other pathologic proteins are deposited in CTE, including amyloid β (Aβ), transactive response (TAR) DNA-binding protein 43 kDa (TDP-43) and α-synuclein.
These findings suggest that a trauma-induced increase in TDP-43 phosphorylation contributes to defective neuronal integrity, and that increasing TSP-1 levels may represent a useful therapeutic approach for the prevention of the neuronal TDP-43 proteinopathy associated with CTE.
Phosphorylation of tau, microglial activation, TAR DNA-binding protein 43 and diffuse axonal injury have all been implicated in the pathogenesis of CTE.
The TDP-43 proteinopathy associated with CTE is similar to that found in frontotemporal lobar degeneration with TDP-43 inclusions, in that widespread regions of the brain are affected.