The patient was a 69 year-old male with a history of waxing and waning cognitive decline. In addition, the patient had visual hallucinations, and significant balance problems with numerous reported falls and a history of a Parkinsonian disorder. He had a limited response to L-Dopa, but had an early good response to Exelon. Past medical history included spinal stenosis, gastroparesis, possible REM sleep disorder, autonomic dysfunction (increased sweating), and kidney stones with numerous kidney infections. Other diseases included myocardial infarction and aspiration pneumonia in 2007. Past social history included playing football in junior high and high school with a history of multiple diagnosed concussions. He also was involved and participated in other contact sports including karate, kick boxing, and was a Golden Gloves boxing coach. In his boxing coach role, he would spar without a helmet, increasing his risk for concussive injury. Finally, the patient was in an automotive accident in 1988 with possible head injury.
On post-mortem examination, the fixed brain weight was 1130 grams. A portion of cerebral dura was available for examination and showed no dural fibrosis and no significant epidural or subdural hemorrhages. There were no old or new subarachnoid hemorrhages. The cerebral gyral pattern was of normal anatomic configuration with moderate cerebral edema, but without masses, vascular abnormalities, or palpable lesions. The left occipital lobe was mildly dusky. There was no evidence of orbital or temporal tip contusions. The cerebral vasculature was ectatic but without atherosclerosis. The circle of Willis had a normal anatomical configuration. The brainstem and cerebellum had a normal external appearance. The spinal dura showed no evidence of epidural hemorrhages and the spinal cord was not distorted by any contained masses or other lesions. Serial coronal sections of the cerebral hemispheres revealed the cortical gray and white matter structures to be without hemorrhages, infarcts, or mass lesions. There was mild atrophy of the anterior hippocampus with moderate atrophy of the posterior hippocampi bilaterally. There was also mild atrophy of the posterior cerebral white matter, which followed the corpus callosum trajectory. The corpus callosum demonstrated mild atrophy as well. The basal ganglia, thalamus, amygdalae, and mamillary bodies bilaterally were of normal size, color and consistency. The ventricular system was moderately dilated with no gradient and was otherwise symmetrical. Serial sections of the brainstem and cerebellum revealed mild superior cerebellar vermal atrophy and mild to moderate cerebellar dentate nucleus atrophy with a dusky gray discoloration. The substantia nigra was thin but did not demonstrate pallor. The locus ceruleus was well pigmented. Serial sections of the spinal cord were symmetrical without discoloration or lesions.
The H&E and Bielschowsky silver stains revealed numerous amyloid plaques of both the diffuse as well as neuritic type in all neocortical areas in laminar arrangement. In addition, there were numerous neurofibrillary tangles, particularly in the pyramidal neurons of layers 3 and 5, but no cortical Lewy bodies were present measured by alpha-synuclein staining (Figure 1). There was marked pallor of the white matter with numerous vessels that were hyalinized. The caudate nucleus and putamen contained diffuse plaques, gliosis, and numerous vessels that were hyalinized. The hippocampus and amygdala contained numerous plaques and neurofibrillary tangles in a laminar distribution. The thalamus contained tangles in the midline nuclei. The substantia nigra was focally gliotic with some neuronal dropout but without evidence of Lewy or pale bodies determined by negative staining for alpha-synuclein. The pons contained tangles in the locus ceruleus and raphe nuclei. The cerebellum contained no diffuse plaques in the molecular layer. Throughout the brain there was retraction artifact surrounding neurons and blood vessels. Immunoperoxidase staining for PHF1/tau revealed numerous neurofibrillary tangles in the cerebral cortex including the temporal lobe, cingulate gyrus, and superior frontal cortex. The overall score for tau changes was at a B3 level (NIA criteria). The PHF/tau also significantly stained the neuritic component of the amyloid plaques and the amyloid plaque score was at a C3 level (NIA criteria). Tau positive tangles were also noted in the raphe and the locus ceruleus. No tau positive tangles were found in the substantia nigra, periaqueductal grey, or in the basis pontis. Ubiquitin stains for Lewy bodies and TDP-43 staining were also negative in the midbrain and pons. The neuropathological findings were consistent with AD Braak stage VI, by the NIA Consensus Criteria. Therefore, because no brainstem or cortical Lewy bodies were indentified with alpha-synuclein staining, the diagnoses of typical idiopathetic Parkinson's disease or diffuse Lewy body disease were ruled out. In addition, no neurofibrillary tangles or tufted astrocytes were found in areas that are usually associated with progressive supranuclear palsy (PSP).