18F-Florzolotau PET Imaging Unveils Tau Pathology in Dementia with Lewy Bodies

Background Dementia with Lewy bodies (DLB) commonly exhibits a complex neuropathology, sharing characteristics with Alzheimer's disease (AD), including tau aggregates. However, studies using the 18F-AV-1451 tau tracer have shown inconsistent findings regarding both the extent and topographical distribution of tau pathology in DLB. Objectives Our aim was to elucidate the topographical patterns of tau deposition in DLB and to investigate the in vivo pathological distinction between DLB and AD in virtue of the 18F-Florzolotau positron emission tomography (PET) imaging. Methods This cross-sectional study enrolled patients with DLB (n = 24), AD (n = 43), and cognitively healthy controls (n = 18). Clinical assessments and 18F-Florzolotau PET imaging were performed. 18F-Florzolotau binding was quantitatively assessed on PET images using standardized uptake value ratios and voxel-wise analysis. Results 18F-Florzolotau PET imaging revealed widespread tau deposition across various cortical regions in DLB, uncovering heterogeneous topographical patterns. Among patients, 54.17% showed patterns similar to AD, whereas 16.67% exhibited distinct patterns. Compared to AD, DLB exhibited a unique in vivo neuropathological profile, characterized by a lower tau protein burden, heterogeneous topographical distributions, and a specific role of the medial temporal lobe in tau pathology. Conclusions 18F-Florzolotau PET imaging elucidated tau pathology patterns in DLB, providing valuable insights for future in vivo pathological differentiation and potential disease-modifying therapies.