Table 2.

Preliminary NINDS criteria for the pathological diagnosis of CTE

Required for diagnosis of CTE
1.	The pathognomonic lesion consists of p-tau aggregates in neurons, astrocytes, and cell processes around small vessels in an irregular pattern at the depths of the cortical sulci

Supportive neuropathological features of CTE
p-Tau-related pathologies:
1.	Abnormal p-tau immunoreactive pretangles and NFTs preferentially affecting superficial layers (layers II–III), in contrast to layers III and V as in AD
2.	In the hippocampus, pretangles, NFTs or extracellular tangles preferentially affecting CA2 and pretangles and prominent proximal dendritic swellings in CA4. These regional p-tau pathologies differ from the preferential involvement of CA1 and subiculum found in AD (Fig. 3)
3.	Abnormal p-tau immunoreactive neuronal and astrocytic aggregates in subcortical nuclei, including the mammillary bodies and other hypothalamic nuclei, amygdala, nucleus accumbens, thalamus, midbrain tegmentum, and isodendritic core (nucleus basalis of Meynert, raphe nuclei, substantia nigra and locus coeruleus)
4.	p-Tau immunoreactive thorny astrocytes at the glial limitans most commonly found in the subpial and periventricular regions
5.	p-Tau immunoreactive large grain-like and dot-like structures (in addition to some threadlike neurites) (Fig. 2h)
Non-p-tau-related pathologies:
1.	Macroscopic features: disproportionate dilatation of the third ventricle, septal abnormalities, mammillary body atrophy, and contusions or other signs of previous traumatic injury
2.	TDP-43 immunoreactive neuronal cytoplasmic inclusions and dot-like structures in the hippocampus, anteromedial temporal cortex and amygdala (Fig. 4)

Age-related p-tau astrogliopathy that may be present; non-diagnostic and non-supportive [22]
1.	Patches of thorn-shaped astrocytes in subcortical white matter
2.	Subependymal, periventricular, and perivascular thorn-shaped astrocytes in the mediobasal regions
3.	Thorn-shaped astrocytes in amygdala or hippocampus [22]