Subcortical tau burden correlates with regional brain atrophy and plasma markers in four-repeat tauopathy parkinsonism.

BackgroundF-florzolotau positron emission tomography (PET) assists in the diagnosis of progressive supranuclear palsy (PSP).ObjectiveWe aimed to investigate the relationship between F-florzolotau uptake and clinical severity, structural volume changes, and plasma markers in four-repeat tauopathies.MethodsA total of 80 participants were recruited: 35 with PSP (11 with PSP-Richardson syndrome and 24 with PSP non-Richardson syndrome), 9 with corticobasal syndrome (CBS), 10 with Alzheimer's disease (AD), 8 with Parkinson's disease, and 18 controls. All participants underwent F-florzolotau PET, brain magnetic resonance imaging (MRI), and plasma biomarker investigation (total and phosphorylated tau [pTau181], neurofilament light chain, and glial fibrillary acidic protein [GFAP]).ResultsF-Florzolotau uptake was significantly higher in the subcortical regions of the pallidum, subthalamic nucleus (STN), midbrain, red nucleus, and raphe nucleus in PSP patients compared to the other groups (all < 0.01). Subcortical tau tracer retention assisted in distinguishing PSP and CBS from controls (AUC = 0.836, < 0.001). Tau tracer retention could differentiate PSP and CBS from AD in cortical (< 0.001) and subcortical regions (= 0.028). The motor severity of PSP positively correlated with tau burden in STN (= 0.044) and substantia nigra (= 0.035). Tau tracer uptake was associated with cortical volume changes in CBS (= 0.031), PSP non-Richardson syndrome (= 0.003), and AD (= 0.044). Cortical tau retention correlated with plasma levels of GFAP (= 0.001) and pTau181 (= 0.036).ConclusionsSubcortical F-Florzolotau uptake assist the diagnosis of 4R tauopathy parkinsonism. Additionally, regional tau burden contributes to structural brain volume changes and correlates with plasma levels of GFAP and pTau181.