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This chapter speaks about a 75-year-old woman admitted with a 4-year history of progressive social withdrawal, decreased fluency, and difficulty handling complex tasks. Magnetic Resonance Imaging (MRI) of the brain showed prominent mesencephalic atrophy, dilation of the third ventricle, and mild cerebral atrophy. Based upon her history and examination, the patient met National Institute of Neurological Disorders and Stroke - Society for Progressive Supranuclear Palsy (NINDS-SPSP) diagnostic criteria for probable Progressive Supranuclear Palsy (PSP). Available data showed that the diagnosis of PSP was pathologically confirmed in essentially 100% of patients who meet these criteria. The patient's motor function progressively worsened, and she died from respiratory complications, approximately 6 years following symptom onset. Progressive supranuclear palsy is a sporadic neurodegenerative disease, which is defined clinicopathologically by the constellation of atypical parkinsonism, supranuclear vertical gaze palsy, and a characteristic pattern of tau accumulation within the brainstem and basal ganglia.