An exploratory ¹⁸F-Florzolotau tau PET study in putative body-first versus brain-first Parkinson's disease.

Abstract

The proposed body-first and brain-first Parkinson's disease (PD) subtypes are classified based on the initial localization of α-synuclein inclusions. Emerging evidence indicates the copathology of α-synuclein and tau in PD. However, the topographical pattern of tau deposition and its difference between these two phenotypes remain unclear. This study aimed to describe the tau deposits via ¹⁸F-Florzolotau PET/CT imaging in PD patients with the putative body-first and brain-first subtypes. A total of ten PD patients with presumed body-first subtypes (PDpRBD+), sixteen PD patients with presumed brain-first subtypes (PDpRBD-), and seventeen healthy controls (HCs) were enrolled. Clinical assessments and ¹⁸F-Florzolotau PET imaging were conducted. ¹⁸F-Florzolotau uptake was higher in the right precuneus and left posterior cingulate regions in the PDpRBD+ group than in the PDpRBD- group. Additionally, ¹⁸F-Florzolotau uptake in the right limbic and paralimbic structures was inversely correlated with Mini-Mental State Examination (MMSE) scores in PD patients with the putative body-first subtype. Our preliminary findings demonstrated distinct ¹⁸F-Florzolotau uptake patterns between the hypothesized PD subtypes. These results provide in vivo evidence of subtype-related differences in tau PET signals, suggesting potential heterogeneity beyond classical α-synuclein pathology, though further validation is warranted.