AimsSince the first description of the classical presentation of progressive supranuclear
palsy (PSP) in 1963, now known as Richardson's syndrome (PSP-RS), several distinct
clinical syndromes have been associated with PSP-tau pathology. Like other neurodegenerative
disorders, the severity and distribution of phosphorylated tau pathology are closely
associated with the clinical heterogeneity of PSP variants. PSP with corticobasal
syndrome presentation (PSP-CBS) was reported to have more tau load in the mid-frontal
and inferior-parietal cortices than in PSP-RS. However, it is uncertain if differences
exist in the distribution of tau pathology in other brain regions or if the overall
tau load is increased in the brains of PSP-CBS. MethodsWe sought to compare the clinical
and pathological features of PSP-CBS and PSP-RS including quantitative assessment
of tau load in 15 cortical, basal ganglia and cerebellar regions. ResultsIn addition
to the similar age of onset and disease duration, we demonstrated that the overall
severity of tau pathology was the same between PSP-CBS and PSP-RS. We identified that
there was a shift of tau burden towards the cortical regions away from the basal ganglia;
supporting the notion that PSP-CBS is a cortical' PSP variant. PSP-CBS also had less
severe neuronal loss in the dorsolateral and ventrolateral subregions of the substantia
nigra and more severe microglial response in the corticospinal tract than in PSP-RS;
however, neuronal loss in subthalamic nucleus was equally severe in both groups. ConclusionsA
better understanding of the factors that influence the selective pathological vulnerability
in different PSP variants will provide further insights into the neurodegenerative
process underlying tauopathies.
