Microglial activation parallels system degeneration in progressive supranuclear palsy and corticobasal degeneration

The role of microglia in progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD) is unknown. To address this issue we examined 10 cases of PSP, 5 cases of CBD, and 4 normal controls. Microglial and tau burdens were determined with image analysis on brain sections that had been immunostained with monoclonal antibodies to HLA-DR and phospho-tau. We found that microglial activation was greater in PSP and CBD than normal controls, and that the microglial burden correlated with the tau burden in most areas. There were distinct patterns of microglial activation and tau pathology in PSP and CBD, with PSP showing more pathology in infratentorial structures and CBD showing more pathology in supratentorial structures. These results support the notion that PSP and CBD are distinct clinicopathologic entities. Microglial activation was not well correlated with tau pathology in the brainstem of PSP, which suggests that brainstem pathology in PSP is not exclusively due to tau pathology. While the results do not necessarily support a direct causal link between microglial activation and neurodegeneration in PSP or CBD, they nevertheless suggest that microglia play a role in disease pathogenesis.