Recent advances in progressive supranuclear palsy: a review

Area of Science:

• Neurology
• Neuroscience
• Genetics

Background:

• Progressive Supranuclear Palsy (PSP) was historically viewed as a uniform disorder characterized by parkinsonism, early falls, vertical gaze palsy, and cognitive decline.
• Recent clinicopathological studies reveal significant heterogeneity within PSP, identifying distinct clinical subtypes.
• Current diagnostic tools rely on neuroimaging and lab findings, but definitive biomarkers for PSP are still lacking.

Purpose of the Study:

• To acknowledge the recognized heterogeneity of Progressive Supranuclear Palsy (PSP).
• To highlight the current limitations in diagnostic biomarkers for PSP.
• To emphasize the role of tau pathology and ongoing genetic research in understanding PSP.

Main Methods:

• Clinicopathological studies have been instrumental in recognizing PSP heterogeneity.
• Analysis of tau-positive aggregates in specific brain regions (basal ganglia, brainstem).
• Investigation of the association between PSP and the H1 tau haplotype.

Main Results:

• PSP presents with diverse clinical subtypes, challenging the notion of a uniform disorder.
• Tau-positive aggregates are a key neuropathological feature, predominantly in the basal ganglia and brainstem.
• A strong association exists between PSP and the H1 tau haplotype, suggesting tau's role.

Conclusions:

• Progressive Supranuclear Palsy is a heterogeneous condition with multiple clinical presentations.
• Tau protein pathology and specific genetic factors, like the H1 haplotype, are implicated in PSP.
• Future research, including genetic studies and genome-wide association studies, is crucial for identifying additional genetic factors and potential biomarkers for PSP.