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.

3H-BU99008 and 3H-Deprenyl showed distinct binding behavior and displayed a diverse array of binding sites (single or multiple) in PD and control brains. Importantly, 3H-BU99008 and 3H-Deprenyl autoradiography studies captured pronounced reactive astrogliosis in PD brain regions, corroborated by marked changes in astrocytic markers, morphology, and cellular processes. Highlights: Astroglial tracers BU99008 and Deprenyl displayed a range of binding sites with different levels of affinity and proportions (%) in healthy control (CN) and Parkinson's disease (PD) brains. Astroglial tracers BU99008 and Deprenyl showed a highly specific (permanent) high-affinity (HA) binding site in the nanomolar range, which might be consistent across different pathologies. Astroglial tracers BU99008 and Deprenyl highlighted distinct tracer binding behavior, indicating that they might be targeting different subpopulations or specific states of astrocytes in CN and PD brains. Astroglial tracers BU99008 and Deprenyl captured prominent reactive astrogliosis at the advanced/end stages of PD, substantiated by a significant increase in intercellular adhesion molecule 1 (ICAM-1)-positive reactive astrocytes and marked changes in astrocytic morphology and processes.

We employed a multi-marker approach and performed in vitro radioligand binding and autoradiography studies with 3H-BU99008 and 3H-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.