A qualitative and quantitative study of grumose degeneration in progressive supranuclear palsy

Grumose degeneration (GD) of the dentate nucleus is a common feature in pro gressive supranuclear palsy (PSP), but its pathogenesis has not been well s tudied, and its clinical significance remains unknown. This report describe s a quantitative study of GD in 9 cases of PSP using image analysis with si ngle- and double-immunolabeling, as well as histochemical stains for myelin and axons. GD was associated with demyelination, axonal loss, glial tau pa thology, and microgliosis in regions juxtaposed to the dentate nucleus (DN) . Specifically, demyelination and microgliosis were prominent in the superi or cerebellar peduncle (SCP), dentate hilus, and cerebellar hemispheric whi te matter. Tau pathology and microgliosis were less prominent in the DN its elf. The degree of myelin loss correlated with the tau burden in the SCP. G AP-43, which is a phosphoprotein known to be involved in axonal growth and sprouting, was decreased in the DN of PSP, and the degree of GAP-43 loss co rrelated with severity of GD. These results suggest that GD may be related to progressive pathology in the dentatorubrothalamic tract as well as the c erebellar hemispheric white matter, and that GD may be a consequence of con current degeneration in both output from and input to the DN. The results f urther suggest a possible role for oligodendroglial and myelin pathology in the pathogenesis of PSP.