The patient was a 41 year-old male with a history of participation in the National Football League for multiple seasons over the course of years. Upon retirement, the patient began to exhibit forgetfulness that was subsequently followed by progressive agitation, depression, anxiety, and agoraphobia in the years prior to his death.
The fixed brain weighed 1554 grams. A portion of the dura was not available for examination. The leptomeninges were thin and translucent over the convexities but over the base of the brain were fibrotic. There was no cerebral edema, and no evidence of contusions at the base of the brain. There was no evidence of cortical atrophy, infarctions or mass lesions. There was mild cerebral edema. The arteries of the circle of Willis demonstrated no atherosclerosis. There were no aneurysmal dilatations of the cerebral vasculature. Subfalcine, transtentorial, uncal, or tonsillar herniation was not appreciated. The brainstem and cerebellum had a normal external appearance. Serial coronal sectioning through the fixed brain revealed the usual internal architectural features without infarcts or mass lesions. The subcortical nuclei including the basal ganglia and thalamus, as well as mammillary bodies bilaterally were of normal size, color, and consistency. There was no evidence of hippocampal or amygdalae atrophy. The posterior corpus callosum showed mild thinning. The ventricular system was mildly dilated. Serial sections of the brainstem and cerebellum revealed no lesions, but the substantia nigra and the pontine locus ceruleus showed moderate pallor.
The H&E and Bielschowsky silver stains revealed no amyloid plaques of either the diffuse or neuritic type in any of neocortical or subcortical areas examined. However, there were neurofibrillary tangles, particularly in the neurons of the superficial temporal neocortex. No cortical Lewy bodies were identified with alpha-synuclein staining. Neurofibrillary tangles were also noted in entorhinal cortex particularly in the origin of the perforant pathway. The hippocampus and amygdala contained neurofibrillary tangles in a diffuse distribution in the latter. Most of the hippocampal CA fields contained diffuse neurofibrillary tangles. The substantia nigra showed no significant neuronal drop out. Lewy bodies were not readily identified in the substantia nigra. The pons contained tangles in the locus ceruleus. PHF-1 tau staining revealed numerous positive tangles and neuritic neuropil changes in the entorhinal cortex including the neurons in the origin of the perforant pathway. In addition, there was PHF-1 tau positive tangles in the superficial neocortical regions (temporal>mid-frontal>>occipital). The amygdala, hippocampus and thalamus contained PHF-tau positive tangles. The substantia nigra contained a single neuron with surrounding neuritic change, but the locus ceruleus (LC) was severely affected with numerous PHF-tau positive tangles and neuritic change in the neuropil. The raphe and the surrounding pontine tegmentum contained a few scattered phosphorylated tau positive cells (Figure 2).