Objective: To explore whether PSP-RS) and PSP-P have different regional tau burden distributions in the brain and whether these distributions are related to motor and cognitive impairment in each subtype.

Background: PSP is characterized pathologically by the accumulation of hyperphosphorylated four-repeat tau protein. While PSP-RS and PSP-P are recognized as the main clinical subtypes, the pathologic mechanisms underlying their clinical distinctions remain unclear.

Method: In the Study of Comprehensive ANd Multimodal Marker-based Cohort of PSP (SCAN-PSP, NCT05579301), we prospectively enrolled patients with PSP from the two referral hospitals between January 2022 and August 2023. PSP subtypes were determined based on the MDS-PSP diagnostic criteria. Patients underwent tau-PET (18F-flortaucipir) scans, and regional comparisons of tau uptake were performed across the whole brain using region-of-interest. Clinical evaluations included the PSPRS, H&Y scale, MMSE, and MoCA.

Results: Forty-nine patients with PSP (29 PSP-RS and 20 PSP-P) were included. Tau uptake did not differ between the PSP groups in cortical areas, basal ganglia, and brainstem. However, when focusing on basal ganglia areas, caudate/STN, putamen/STN, and pallidum/STN ratios were significantly lower in the PSP-RS group than in the PSP-P group, indicating the relative higher tau burden in the STN compared to other basal ganglia area in the PSP-RS group. Significant correlations in the PSP-P group included PSPRS total score with pallidum, STN, and pallidum tau uptake, H&Y stage with pallidum and STN tau uptake, MMSE with lower STN tau uptake, and MoCA with lower pallidum and STN tau uptake. Conversely, no significant correlation was found between tau uptake and clinical markers in the PSP-RS group.

Conclusion: Although tau burden in the brain appeared grossly similar between PSP-RS and PSP-P, the relative tau burden in the STN compared to other basal ganglia regions may differ between the two subtypes. Tau accumulation within specific basal ganglia regions may reflect the severity of motor and cognitive impairment in PSP-P subtype, but not in PSP-RS subtype. Further multimodal functional and structural imaging investigations are necessary to assess how distinctive tau accumulation patterns in the basal ganglia influence the clinical manifestations of PSP.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/regional-tau-burden-patterns-and-their-associations-with-clinical-severity-in-progressive-supranuclear-palsy-psp-richardsons-syndrome-and-psp-predominant-parkinsonism-a-prospective-cohort/