Table 1.

McKee CTE Stage Criteria

	Mild Disease		Severe Disease
	Stage I	Stage II	Stage III	Stage IV
P- Tau Pathology
	One or two cortical pathognomonic regions usually in frontal lobe Pathognomonic lesions consist of foci of p-tau NFTs and thread and dot-like neurites Sparse NFTs in locus coeruleus	Three or more pathognomonic lesions affecting multiple cortical regions Pathognomonic lesions consist of foci of p-tau NFTs and thread and dot-like neurites Superficial NFTs in neocortex NFTs in locus coeruleus and nucleus basalis of Meynert	Pathognomonic lesions in multiple cortical regions Pathognomonic lesions consist of foci of p-tau NFTs, thread and dot-like neurites, and astrocytes Clusters of p-tau at depth of sulcus may be larger Superficial neocortical NFTs NFTs in hippocampus, entorhinal and perirhinal cortices, and amygdala NFTs in substantia nigra and locus coeruleus, thalamus, hypothalamus, nucleus basalis of Meynert	Pathognomonic lesions in multiple cortical regions Pathognomonic lesions consist of foci of p-tau NFTs, thread and dot-like neurites, and astrocytes NFTs distributed throughout the neocortex Neocortical astrocytic p-tau pathology may be prominent Neuronal loss and gliosis in the frontal and temporal cortices Severe neurofibrillary degeneration of the medial temporal lobe Neuronal loss and gliosis in medial temporal lobe Severe neurofibrillary degeneration in diencephalon, including mammillary bodies, and brainstem NFTs in cerebellar dentate, basis pontis and spinal cord. Other pathologies, including myelin and axonal loss and TAR DNA-binding protein 43 (TDP-43) pathology

Neuropathological diagnosis of CTE was made using criteria defined by the 2016 NINDS-NIBIB Consensus Conference with modifications. The 2015 panel defined the pathognomonic lesion of CTE as “an accumulation of abnormal hyperphosphorylated tau (p-tau) in neurons and astroglia distributed around small blood vessels at the depths of cortical sulci and in an irregular pattern.” For this study, the neuropathological diagnosis of CTE required the presence of at least one pathognomonic p-tau lesion in the cortex and purely astrocytic perivascular p-tau lesions were considered non-diagnostic. Supportive features for the diagnosis of CTE included neurofibrillary tangles (NFTs) in superficial cortical layers (layers II/III) of the cerebral cortex and pretangles, NFTs or dendritic dystrophy in CA2 and CA4 of the hippocampus.