Relationships Between Glymphatic System Activity and Tau Burden, Dopaminergic Impairment, Abnormal Glucose Metabolism in Progressive Supranuclear Palsy

Abstract

Background

Progressive supranuclear palsy (PSP) is a primary tauopathy characterized by dopaminergic impairment and abnormal glucose metabolism. The glymphatic system can promote the elimination of tau protein. The association between glymphatic function and pathological hallmark in neuroimaging remains unknown.

Methods

Diffusion tensor imaging (DTI) and positron emission tomography (PET) scanning with ¹⁸F-Florzolotau, ¹⁸F-FPCIT, and ¹⁸F-FDG were performed in PSP patients. DTI analysis along the perivascular space (ALPS) index was computed to assess glymphatic function, while the semi-quantitative value was employed to measure tau burden and dopaminergic impairment. The PSP-related pattern (PSPRP) served as an indicator of abnormal metabolic brain network activity.

Results

PSP patients exhibited changes in ALPS index and tau deposition. ALPS index, tau deposition, and PSPRP expression showed significant correlations with clinical scores. Additionally, ALPS index was correlated with tau deposition and PSPRP expression. However, neither ALPS index nor the clinical scores were correlated with striatum dysfunction. Finally, tau deposition in subcortical regions and PSPRP expression exhibited mediating effects between ALPS index and clinical scores.

Conclusion

The glymphatic dysfunction is associated with tau deposition and abnormal metabolic brain network activity and is independent of dopaminergic impairment in PSP.