Tau network topology in progressive supranuclear palsy variants as elucidated by [¹⁸F]PI-2620 PET

Ziel/Aim Progressive supranuclear palsy (PSP) is primary tauopathy with different phenotypic manifestations. The Richardson’s syndrome (PSP-RS) is the most common phenotype, followed by PSPs with predominant parkinsonian (PSP-P) and frontal presentations (PSP-F). Although the pallido-nigro-luysian axis is commonly affected in all PSP, neuropathological studies indicate variations of tau pathology between subtypes. The next-generation tau PET tracer [¹⁸F]PI-2620 seems to enable in vivo mapping of tau pathology in PSP. This study aimed to assess tau network topology in PSP-RS and non-RS individuals using graph theory analysis.

Methodik/Methods Fourteen PSP-RS (age 73.1±5.4 years) and ten non–RS PSP patients (age 67.6±7.3 years) with predominantly PSP-P and PSP-F underwent 60 min. dynamic [¹⁸F]PI-2620 PET imaging. Distribution volume ratios (DVRs) were estimated using non-invasive pharmacokinetic modeling. The tau network was built with nodes representing mean DVRs in 82 cortical/subcortical brain regions. The edges were calculated as Pearson's partial correlation coefficient between pairs of nodes. Student’s t-test and non-parametric permutation test were used, respectively, to assess between-group and network properties. The nodal network results were adjusted for false discovery rate (FDR).

Ergebnisse/Results Regional [¹⁸F]PI-2620 DVRs and global network measures displayed no significant variation between PSP-RS and non-RS groups. The nodal measures of tau network showed significant differences in nodal properties (p_FDR<0.05) resulting in decreased path-length and eccentricity, and increased closeness centrality in multiple brain regions for PSP-RS vs. non-RS PSP patients. We also found that nodal local efficiency and clustering coefficient were increased in the subthalamic nuclei of PSP-RSs compared to non-RS PSPs (pFDR<0.05).

Schlussfolgerungen/Conclusions Applying tau network analysis to quantitative [¹⁸F]PI-2620 PET data, we provide preliminary evidence for the tau network being differently organized in different PSP variants at the nodal level. Enlarging our cohort, ideally also with other PSP subtypes, is desired to investigate whether this approach has potential as an imaging classifier for different PSP subtypes.

Publication History

Article published online:
14 April 2022