Argyrophilic Grain Disease Clinically Presenting as Progressive Supranuclear Palsy with Progressive Gait Freezing

Argyrophilic grain disease (AGD) is a four-repeat tauopathy characterized by the accumulation of argyrophilic grains. Its primary clinical manifestation is late-onset amnestic dementia. While the extension of argyrophilic grains to the substantia nigra may be related to its potential association with parkinsonism, biochemical analyses are lacking.

To elucidate the extent of AGD to the midbrain, including the substantia nigra, using histopathological examination and biochemical analysis in a pathologically proven case of AGD presenting with parkinsonism and cognitive impairment.

We describe the case of a patient suggestive of progressive supranuclear palsy. Neuropathological and biochemical investigations were performed.

Neurological examination of an 80-year-old man with a 6-year history of gait disturbance revealed parkinsonism, including gait freezing, postural instability, bradykinesia, and cognitive impairment. The patient was diagnosed with progressive supranuclear palsy with progressive gait freezing. Five years later, the patient reported falling backward repeatedly, became wheelchair-bound, and died of pneumonia. Macroscopic observations revealed marked amygdala atrophy. Microscopic findings revealed argyrophilic grains in the limbic system, compatible with Saito stage III, as well as in the substantia nigra and midbrain tegmentum. Western blotting showed an AGD-specific band pattern, and immunoelectron microscopy analyses showed an AGD-specific tau filament of abnormally phosphorylated tau in both the nucleus accumbens and midbrain.

This report further confirmed that AGD presents with parkinsonism, commensurate with AGD pathology and biochemical findings extending to the midbrain. Therefore, AGD should be considered in the differential diagnosis of cases presenting with parkinsonism and cognitive impairment in the older population.