| Stage I | No brain atrophy, otherwise unremarkable | Focal epicenters of perivascular p-tau NFT and astrocytic tangles, most prominent in the sulcal depths and typically affecting superior and dorsolateral frontal cortices |
| Stage II | Mild enlargement of the frontal horn of the lateral ventricles or third ventricle, small cavum septum and pallor of the locus coeruleus and substantia nigra | Multiple discrete foci of the cortex, most commonly superior, dorsolateral, lateral, inferior and subcallosal frontal, anterior, inferior and lateral temporal, inferior parietal, insular and septal cortices Moderate densities of neurofibrillary tangles were also found in the locus coeruleus, nucleus basalis of Meynert and amygdala Low densities of p-tau NFT and pretangles in the hypothalamus, CA1 of hippocampus, entorhinal cortex, thalamus, substantia nigra and dorsal and median raphe nuclei of the midbrain |
| Stage III | Mild cerebral atrophy with dilation of the lateral and third ventricles,septal abnormalities including cavum septum pellucidum, septal perforations , and depigmentation the locus coeruleus and substantia nigra, atrophy of the mammillary bodies, thalamus and hypothalamus and thinning of the corpus callosum | Widespread throughout the neocortex, superior frontal, dorsolateral frontal, inferior orbital, septal, insular, temporal pole, superior middle and inferior temporal and inferior parietal cortices, hippocampus, entorhinal cortex, amygdala, nucleus basalis of Meynert and locus coeruleus, olfactory bulbs, hypothalamus, mammillary bodies, substantia nigra and dorsal and median raphe nuclei |
| Stage IV | Atrophy of the cerebral cortex and white matter and marked atrophy of the medial temporal lobe, thalamus, hypothalamus and mammillary body, Mean brain weight was significantly smaller than lower stage CTE and ventricular enlargement, a sharply concave contour of the third ventricle, cavum septum pellucidum and septal perforations or septal absence. Pallor of the locus coeruleus and substantia nigra | Striking neuronal loss in the cortex, hippocampal sclerosis affecting CA1 and subiculum and astrocytic p-tau pathology Widely distributed p-tau abnormalities throughout the cerebrum, diencephalon, basal ganglia, brainstem and spinal cord Primary visual cortex was relatively spared |
