Progressive supranuclear palsy and corticobasal degeneration: lumping versus splitting

Abstract

Progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD) are both sporadic disorders with tau pathology. Criteria have been defined that in most instances allow for adequate diagnosis of the two disorders both clinically and neuropathologically; however, overlap is not uncommon. For example, patients with PSP may present with severe unilateral apraxia and supranuclear gaze palsy can occur in CBD. Pathological overlap also occurs and pathologically "mixed" cases are encountered. Common to both these two tauopathies is that isoforms of four-repeat tau due to splicing of exon 10 define the tau filamentous aggregates. This is in contrast to other tau disorders such as Pick's with three-repeat tau aggregates. Additional evidence for a causal link between PSP and CBD is the finding that both disorders are homozygous for the H1 tau haplotype. Furthermore, in some families with parkinsonism linked to defined mutations of the tau gene (FTDP-17), involved relatives have presented with PSP whereas others with the CBD phenotype. Although PSP and CBD frequently can be clearly separated clinically and pathologically, the degree of clinicopathological and genetic overlap is important and suggests that they represent different phenotypes of the same disorder, with differences occurring perhaps in relation to different genetic background. That PSP and CBD are distinct nosological entities occurring in patients with similar genetic predisposition cannot be ruled out.