Figure 3.

The four stages of CTE. In stage I CTE, p-tau pathology is restricted to discrete foci in the cerebral cortex, most commonly in the superior, dorsolateral or lateral frontal cortices, and typically around small vessels at the depths of sulci (black circles). In stage II CTE, there are multiple epicentres at the depths of the cerebral sulci and localized spread of neurofibrillary pathology from these epicentres to the superficial layers of adjacent cortex. The medial temporal lobe is spared neurofibrillary p-tau pathology in stage II CTE. In stage III, p-tau pathology is widespread; the frontal, insular, temporal and parietal cortices show neurofibrillary degeneration with greatest severity in the frontal and temporal lobe, concentrated at the depths of the sulci. Also in stage III CTE, the amygdala, hippocampus and entorhinal cortex show neurofibrillary pathology. In stage IV CTE, there is severe p-tau pathology affecting most regions of the cerebral cortex and the medial temporal lobe, sparing calcarine cortex in all but the most severe cases. All images, CP-13 immunostained 50-µm tissue sections.