Progressive supranuclear palsy and corticobasal degeneration.

Abstract

Progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD) are sporadic neurodegenerative disorders of mid to late adult life that have shared clinical and pathologic features, but also notable differences that warrant their separation as clinicopathologic entities. Among shared clinical features are extrapyramidal signs similar to Parkinson's disease, but neither PSP nor CBD is responsive to levodopa therapy. Motor abnormalities in PSP are usually symmetrical, whereas asymmetry is the hallmark of CBD. Focal cortical signs, such as apraxia and aphasia, are common in CBD, but rare in PSP. Dementia is more common in CBD than PSP. Severe vertical gaze palsy early in the disease course is common in PSP, but is uncommon or a late manifestation of CBD. Pathologically, both PSP and CBD are associated with neuronal and glial filamentous inclusions that are composed of tau protein. The morphology of neuronal and glial lesions differs in PSP and CBD, but there are a number of lesions with transitional or overlapping features. Distribution of the lesions shows considerable overlap, but the overall distribution of the lesions differs in PSP and CBD. Cortical gray and white matter lesions are prominent in CBD, whereas deep gray matter lesions are more common in PSP. Biochemical studies of brain tissue from PSP and CBD show similar alterations in tau protein. Abnormal tau proteins in PSP and CBD are relatively insoluble and hyperphosphorylated. Furthermore, they appear to be composed of tau enriched in specific tau mRNA splice forms, specifically tau derived from alternative spicing of exon 10, which generates tau with four repeat regions in the microtubule-binding domain. It is unclear if this is due to disease-related differential expression of these tau isoforms, involvement of cell types that express these isoforms preferentially, or selective assembly of these specific tau isoforms in the lesions. Both PSP and CBD are considered to be nonfamilial or sporadic “tauopathies,” but genetic studies suggest that polymorphisms in the tau gene may confer some degree of genetic risk for these disorders. Given the relative rarity of these conditions, further clinical and pathologic studies are needed to define the diagnostic boundaries and to develop biologic markers for their clinical and pathologic differentiation.