A 48-year-old Japanese woman experienced slow-onset
parkinsonism and speech disturbances. Neurological examinations revealed rigidity in the trunk and extremities,
bradykinesia and postural instability, although
cognitive impairments and psychiatric symptoms were not apparent in the early disease stage. Neuroimaging revealed progressive bilateral frontotemporal lobe
atrophy with cerebral blood flow hypoperfusion. No apparent signs of lower motor neuron involvement were observed, such as
fasciculation or electromyogram findings. She eventually reached the
akinetic mutism state, and
gastrostomy and
tracheotomy were performed at 4 years after onset. A clinical diagnosis of
progressive supranuclear palsy was made prior to her death, which occurred 6 years after onset. Post mortem examinations revealed that the brain weighed 1200 g and showed
atrophy of the frontotemporal lobe and brainstem. Severe neuron loss and
gliosis were observed in the frontotemporal lobe. The superior and middle frontal gyri were the most severely affected and showed spongiform changes in the superficial layer. The globus pallidus, subthalamic nucleus, cerebellar dentate nucleus, substantia nigra and inferior olivary nucleus also showed neuronal loss with
gliosis. Using hyperphosphorylated tau (AT-8) immunostaining, pretangle-like neurons, numerous short threads and glial tau pathology were extensively observed. Using Gallyas-Braak
silver staining, thin and short threads were also extensively observed, but considerably fewer than those observed by AT-8 immunostaining. Neither astrocytic plaques nor tuft-shaped astrocytes were observed. Examination by immunoelectron microscopy showed straight fibrils approximately 15 nm in diameter in the neuronal cytoplasmic inclusions in the cerebral cortex and in the fibrillary structures in the cerebral white matter. Western blot analysis of
sarkosyl-insoluble tau revealed predominantly four-repeat tau and a banding pattern similar to that seen in
progressive supranuclear palsy. No pathogenic mutations were found during the gene analysis of
microtubule-associated protein tau. After completing our comprehensive investigation, we diagnosed this patient with unclassifiable four-repeat
tauopathy.