Astrocytes expressing Vitamin D-activating enzyme identify Parkinson's disease

Introduction: Astrocytes are involved in Parkinson's disease (PD) where they could contribute to alpha-Synuclein pathology but also to neuroprotection via alpha-Synuclein clearance. The molecular signature underlying their dual role is still elusive. Given that vitamin D has been recently suggested to be protective in neurodegeneration, the aim of our study was to investigate astrocyte and neuron vitamin D pathway alterations and their correlation with alpha-Synuclein aggregates (ie, oligomers and fibrils) in human brain obtained from PD patients. Methods: The expression of vitamin D pathway components CYP27B1, CYP24A1, and VDR was examined in brains obtained from PD patients (Braak stage 6; n = 9) and control subjects (n = 4). We also exploited proximity ligation assay to identified toxic alpha-Synuclein oligomers in human astrocytes. Results: We found that vitamin D-activating enzyme CYP27B1 identified a subpopulation of astrocytes exclusively in PD patients. CYP27B1 positive astrocytes could display neuroprotective features as they sequester alpha-Synuclein oligomers and are associated with Lewy body negative neurons. Conclusion: The presence of CYP27B1 astrocytes distinguishes PD patients and suggests their contribution to protect neurons and to ameliorate neuropathological traits.