Cerebellar cortical tau pathology in progressive supranuclear palsy and corticobasal degeneration

Abstract.

Immunohistochemical localization of tau in the cerebellar cortex was carried out using a mouse monoclonal antibody against phosphorylation-dependent tau (AT8) in brain tissue (cerebellum) from 13 patients with progressive supranuclear palsy (PSP), 7 patients with corticobasal degeneration (CBD) and 5 age-matched control subjects. Purkinje cell somata that showed diffuse granular accumulation of cytoplasmic tau were found occasionally in 9 of the 13 patients with PSP (69%) and in 4 of the 7 patients with CBD (57%). Tau-positive doughnut-shaped structures were also found occasionally in the cerebellar molecular layer in 6 of the 13 patients with PSP (46%) and 2 of the 7 patients with CBD (29%). No tau immunoreactivity was detected in the cerebellar cortex in the control tissue. In the tissue from one patient with PSP, we also performed a double-labeling immunofluorescence study with anti-glial fibrillary acidic protein (GFAP) antibody and AT8, as well as an immuno-electron microscopic study with AT8. In tau-positive Purkinje cell somata and dendrites, the reaction product was localized mainly within the rough endoplasmic reticulum and free ribosomes. Tau-positive doughnut-shaped structures were located in the GFAP-positive radial processes of Bergmann's glia and were present in the outer areas of inclusions reminiscent of Lewy bodies, which consist of aggregated pathological tau filaments. In conclusion, we have demonstrated a novel tau pathology that affects Purkinje cells and Bergmann's glia in patients with PSP and CBD, indicating that the cerebellar cortex can be involved in the disease processes in PSP and CBD.