Parkinson’s Disease is the second most common neurodegenerative disease and is characterized by neurodegeneration in various areas of the brain, most notably in the substantia nigra. Neuroinflammation and, more specifically, the activation of microglia in the substantia nigra is suggested to play an important role in the pathological processes of Parkinson’s Disease. Upon activation, microglia may adopt a stimulus-dependent phenotype, that can be pro-inflammatory, or more anti-inflammatory. To gain more insight into the actual inflammatory status of affected brain regions in Parkinson’s Disease it is, therefore, important to identify the different microglial phenotypes present.

Accordingly, the aim of this study was to investigate the distribution of different microglia phenotypes present in post-mortem substantia nigra tissue of control, Incidental Lewy Body Disease and Parkinson’s Disease cases using semi-quantitative immunohistochemical analysis of microglia phenotype-specific markers. Our results show an increase in the number of anti-CD68 and anti-class II human leukocyte antigen antibody immunoreactive amoeboid microglia in the substantia nigra of Parkinson’s Disease cases compared to Incidental Lewy Body Disease and control cases, while no differences were found in the number of anti-Ionized calcium-binding adaptor molecule 1- and class II human leukocyte antigen antibody immunoreactive microglia. In addition, no differences were found in the number of anti-transmembrane protein 119- and anti-Purinergic Receptor P2Y12 antibody immunoreactive microglia, suggesting that microglia phenotype present in the SN remains relatively constant between the control, incidental Lewy Body Disease and Parkinson’s Disease cases. Together, our results suggest a subtle switch of part of the microglia population in the substantia nigra of Parkinson’s Disease cases to a specific morphologic phenotype indicative of enhanced lysosomal activity. Although usually interpreted as expression of a pro-inflammatory condition, further characterization of the functional status of this subtype of amoeboid microglia may provide better insight into the role of neuroinflammation in PD pathogenesis.