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

Nature Clinical Practice Neurology volume 2, pages 658–665 (2006)Cite this article

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.

Key Points

  • Traditionally, frontotemporal lobar degeneration (FTLD), progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD) have been distinguishable on the basis of presenting clinical symptoms

  • Recently, molecular and genetic findings have suggested a link between the three disorders

  • PSP and CBD cases show tau inclusions post-mortem, as do some FTLD cases

  • Progressive nonfluent aphasia, a subtype of FTLD, often leads to PSP and CBD

  • Not all FTLD cases are tauopathies

  • As there are currently no treatments available that target the molecular and genetic etiologies of these three disorders, they should continue to be considered distinct

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Figure 1: Venn diagram summarizing the similarities and differences between corticobasal degeneration, progressive supranuclear palsy and frontotemporal lobar degeneration.

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Acknowledgements

This work was supported by the Larry L Hillblom Foundation, National Institute on Aging grant P01-AG1972403, and an Alzheimer's Disease Research Center grant P50-AG023501.

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Authors and Affiliations

  1. intern in internal medicine at California Pacific Medical Center,

    Sharon Sha, Craig Hou, Indre V Viskontas & Bruce L Miller

  2. neurology physician at Kaiser Permanente Hospital,

    Sharon Sha, Craig Hou, Indre V Viskontas & Bruce L Miller

  3. postdoctoral fellow at the Memory and Aging Center at the University of California, San Francisco (UCSF),

    Sharon Sha, Craig Hou, Indre V Viskontas & Bruce L Miller

  4. Professor of Neurology, holds the AW & Mary Margaret Clausen Distinguished Chair, and is clinical director of the Memory and Aging Center at UCSF, San Francisco, CA, USA

    Sharon Sha, Craig Hou, Indre V Viskontas & Bruce L Miller

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Correspondence to Bruce L Miller.

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Sha, S., Hou, C., Viskontas, I. et al. Are frontotemporal lobar degeneration, progressive supranuclear palsy and corticobasal degeneration distinct diseases?. Nat Rev Neurol 2, 658–665 (2006). https://doi.org/10.1038/ncpneuro0357

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