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 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.