Evaluation of the specificity of the central diagnostic criterion for chronic traumatic encephalopathy

Chronic traumatic encephalopathy (CTE) is a postmortem diagnosis. Consensus postmortem, but not antemortem, diagnostic criteria have been established. A key factor in these criteria is evidence of phosphorylated-tau (p-tau) around sulcal vessels in the cortex. However, this sign has been observed anecdotally in a diverse range of neurodegenerative diseases (NDD). We therefore hypothesise that this criterion may lack specificity.

To test this, we assessed patients with NDD, but no documented history of brain trauma, for sulcal p-tau. Tissue was retrieved from Dublin Brain Bank (known NDD n = 17; control with no diagnosed NDD n = 6; CTE n = 1), and slides were prepared from three sites with a predilection for trauma: superior frontal gyrus, temporal pole, and superior temporal gyrus. We stained the resulting anonymised slides with both hemotoxylin and eosin (H&E) and p-tau. Three neuropathologists, blinded to the clinical history and neuropathological diagnosis in each instance, evaluated each case for sulcal p-tau. We calculated the interrater agreement, using Fleiss's kappa, and the specificity of this neuropathological sign.

Sulcal p-tau was highly specific to diagnosed CTE cases (specificity 0.98), with moderate interrater agreement (κ = 0.45).

In conclusion, therefore, we observed sulcal p-tau to be a sign highly specific to CTE when compared with NDD cases in the absence of head trauma.