Pathophysiology, genetics, clinical features, diagnosis and therapeutic trials in progressive supranuclear palsy

Introduction: Progressive supranuclear palsy (PSP) is an atypical parkinsonian syndrome formally recognized in 1964. Historically considered sporadic, recent research has shown genes strongly associated with PSP. Pathologically, it is characterized by aggregated tau protein forming neurofibrillary tangles in predominantly subcortical neurons, tufted astrocytes and oligodendroglial inclusions. Patients typically present with progressive parkinsonism, ocular motility disturbances and early falls. Although rare in the general population, it is the most common atypical parkinsonian disorder - approximately 6% of all parkinsonian patients evaluated at a specialty clinic are diagnosed with PSP. Areas covered: A relentlessly progressive neurodegenerative disorder, PSP is still commonly misdiagnosed. Genetic studies continue to provide insight into the pathophysiology of PSP, guiding future therapeutic trials. This paper summarizes the history, clinical features and subtypes, diagnostic criteria, neuroimaging, pathophysiology, genetic studies, current and future therapeutic trials in PSP. Expert opinion: As PSP becomes more widely recognized and imaging modalities continue to advance, clinical diagnostic accuracy should improve. Currently, no proven disease-modifying agents are available for parkinsonian disorders such as PSP. Biochemical analysis of genes associated with PSP may elucidate how mutations impact brain cells, in hopes of directing future trials of disease-modifying agents and symptomatic therapeutic intervention.