Are frontotemporal lobar degeneration, progressive supranuclear palsy and corticobasal degeneration distinct diseases?

Abstract

New findings relating to the clinical, genetic and molecular bases of neurodegenerative disorders have led to a shift away from traditional nomenclatures of clinical syndromes. Historically, frontotemporal lobar degeneration (FTLD), corticobasal degeneration (CBD) and progressive supranuclear palsy (PSP) were classified on the basis of distinct clinical and pathological features. In recent years, however, advances in molecular and genetic research have led clinicians to suggest that the similar etiologies of the three disorders warrant their amalgamation into a single disorder with three subtypes. In this Review, we consider the utility and validity of combining FTLD, CBD and PSP. The earliest reports of these disorders demonstrate their distinctiveness, whereas recent findings challenge traditional nomenclatures by showing etiological overlap. For example, tau inclusions have been confirmed in patients with CBD and those with PSP, and in some patients with FTLD, implying that all three disorders are 'tauopathies'. Furthermore, most patients with progressive nonfluent aphasia, a subtype of FTLD, show PSP or CBD post-mortem. Even tau-related cases of FTLD, CBD and PSP are distinguishable on the basis of other criteria, however, and many FTLD cases do not show tau pathology. We argue, therefore, that FTLD, CBD and PSP should be considered as pathologically similar but distinct syndromes. New research criteria for CBD and PSP should note that progressive nonfluent aphasia is often a precursor of these conditions.