White matter pathology in progressive supranuclear palsy (PSP): a quantitative study of 8 cases

Aims. To quantify white matter pathology in progressive supranuclear palsy (PSP). Material: Histological sections of white matter of 8 PSP and 8 control cases. Method: Densities and spatial patterns of vacuolation, glial cell nuclei, and glial inclusions (GI) were measured in 8 cortical and subcortical fiber tracts. Results: No GI were observed in control fiber tracts. Densities of vacuoles and glial cell nuclei were greater in PSP than in controls. In PSP, density of vacuoles was greatest in the alveus, frontopontine fibers (FPF), and central tegmental tract (CTT), and densities of glial cell nuclei were greater in cortical than subcortical regions. The highest densities of GI were observed in the basal 'ganglia, FPF, cerebellum, and superior frontal gyms (SFG). Vacuoles, glial cells and GI were distributed randomly, uniformly, in regularly distributed clusters, or in large clusters across fiber tracts. GI were more frequently distributed in regular clusters than the vacuoles and glial cell nuclei. Vacuoles, glial cell nuclei, and GI were not spatially correlated. Conclusions: The data suggest significant degeneration of white matter in PSP, vacuolation being related to neuronal loss in adjacent gray matter regions, GI the result of abnormal tau released from damaged axons, and gliosis a response to these changes.