Table 2.

Typical microscopic and macroscopic features found in each stage of CTE.

Stage	Typical Macroscopic appearance	Typical Microscopic appearance
I	Unremarkable gross appearance and weight Occasional enlargement of frontal horns of the lateral ventricles	One of two, Isolated perivascular foci of p-tau NFT and neurites, the neurites are often dotlike; the perivascular foci are commonly found at the depths of the sulcus of the superior and dorsolateral frontal and temporal cortices p-tau NFTs may be found in the locus coeruleus
II	Unremarkable appearance and weight Pallor of the locus coeruleus and substantia nigra Enlargement of the frontal horns of the lateral ventricles	Multiple (> 3) perivascular foci of p-tau NFTs in the frontal, temporal or parietal cortices NFTs in the superficial cortical layers of cortex, especially in the temporal lobe p-tau NFTs in the locus coeruleus, substantia nigra and substantia innominata Sparse TDP-43 positivity in medial temporal lobe
III	Mildly reduced brain weight, atrophy in the frontal and temporal lobes Enlargement of the third and lateral ventricles Septal abnormalities, ranging from mild septal perforation to complete atrophy Atrophy of the thalamus, hypothalamus, posterior corpus callosum and mammillary bodies depigmentation of the locus coeruleus and substantia nigra	NFT pathology in widespread cortical regions NFTs in the locus coeruleus, substantia nigra, subs innominata Diffuse NFTs and neurites in hippocampus, amygdala, and entorhinal cortex Sparse NFT in the thalamus, nucleus accumbens TDP-43 positivity in the cerebral cortex, and medial temporal lobe
IV	Significantly reduced brain weight Extensive atrophy throughout the brain, including white matter Significant enlargement of the third and lateral ventricles Marked septal abnormalities, as in stage III Severe pallor of the locus coeruleus and substantia nigra in all cases	Diffuse white matter rarefaction Dense p-tau NFT and glial pathology distributed throughout the brain (cerebrum, diencephalon, basal ganglia, and brainstem) and spinal cord Marked NFT in medial temporal lobe structures NFT in LC, SN, SI NFT in basis pontis, mammillary bodies, dentate nucleus of cerebellum TDP-43 inclusion bodies and neurites in cortex, medial temporal lobe, brainstem

Note: This is not the criteria used for making the staging designation (refer to Table 1). Adapted from (56) with permission.