Neuropathology of variants of progressive supranuclear palsy

Abstract

Neurodegenerative tauopathies, of which progressive supranuclear palsy (PSP) is one of the most common, are clinically heterogeneous, reflecting differences in distribution and biochemical composition of tau pathology. This review highlights the range of clinical and pathologic presentations of PSP and its variants. Progressive supranuclear palsy is a 4R tauopathy with neuronal and glial tau-immunoreactive lesions in neuroanatomically specific nuclei in the basal ganglia, diencephalon, brainstem and cerebellum, with restricted involvement of the neocortex. Hierarchical cluster analyses of clinical and pathologic features of PSP indicate that there are distinct clinicopathologic variants of PSP. In variants of PSP presenting with focal cortical syndromes, such as frontotemporal dementia, corticobasal syndrome and apraxia of speech, there is greater cortical pathology than in typical PSP. In variants of PSP presenting with levodopa-responsive Parkinsonism, as well as pure akinesia and gait failure, there is less cortical pathology and more severe degeneration in the cardinal nuclei - globus pallidus, subthalamic nucleus and substantia nigra - than in typical PSP. Clinical variants in PSP reflect varying anatomical distribution of tau pathology, but they share histopathologic, biochemical and genetic features with typical PSP. The basis for anatomical selective vulnerability in PSP and its variants remains to be determined.