Stage IV chronic traumatic encephalopathy. In stage IV chronic traumatic encephalopathy, there is widespread phosphorylated tau (p-tau) pathology affecting most regions of the cerebral cortex and medial temporal lobe with relative sparing of the calcarine cortex. Astrocytic tangles are prominent and there is marked neuronal loss in the cortex, amygdala and hippocampus. p-tau neurofibrillary tangles (NFTs) are reduced in size and density. The cortical epicenters show severe neuronal loss and prominent astrocytic tangles (A); similar changes are found throughout the frontal, temporal and parietal cortices (B). The nucleus basalis of Meynert shows marked neurofibrillary pathology and gliosis (C). The amygdala demonstrates intense gliosis and p-tau neuronal and glial degeneration (D). The hippocampus is sclerotic with marked neuronal loss, gliosis, ghost NFTs and astrocytic tangles (E). CP-13-immunostained 50 μm tissue sections, some counterstained with cresyl violet. Scale bar = 100 μm. Adapted from .