Mapping reactive astrogliosis in Parkinson's brain with astroglial tracers BU99008 and Deprenyl: New insights from a multi-marker postmortem study

BACKGROUND: Despite significant astrocytic involvement in Parkinson's disease (PD), the knowledge regarding the role of reactive astrogliosis is still at the surface level; largely due to lack of specific biomarkers to track these processes. Novel astroglial PET-tracers BU99008 and Deprenyl, hold immense potential for visualizing reactive astrogliosis in PD. However, they have not been thoroughly investigated in PD. METHODS: We employed a multi-marker approach and performed in vitro radioligand binding and autoradiography studies with H-3-BU99008 and H-3-Deprenyl together with astrocytic immunofluorescence and morphometric analyses in the frontal cortex, temporal cortex, caudate and putamen brain regions of PD (n = 4) and control (n = 7) cases. RESULTS AND DISCUSSION: H-3-BU99008 and H-3-Deprenyl showed distinct binding behavior and displayed a diverse array of binding sites (single or multiple) in PD and control brains. Importantly, H-3-BU99008 and H-3-Deprenyl autoradiography studies captured pronounced reactive astrogliosis in PD brain regions, corroborated by marked changes in astrocytic markers, morphology, and cellular processes.