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Novel Types of Frontotemporal Lobar Degeneration: Beyond Tau and TDP-43

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Abstract

Most cases of frontotemporal lobar degeneration (FTLD) are characterized by the abnormal accumulation of either the microtubule-associated protein tau or the transactive response DNA-binding protein with Mr 43 kDa, TDP-43 (FTLD-tau and FTLD-TDP, respectively). However, there remain ∼10% of cases, composed of a heterogenous collection of uncommon disorders, for which the molecular basis remains uncertain. In this review, we describe the characteristic genetic, clinical, and pathological features of the major tau/TDP-negative FTLD subtypes, with focus on recent advances in our understanding of their molecular basis. This includes the discovery that the pathological changes in atypical FTLD with ubiquitinated inclusions, neuronal intermediate filament inclusion disease, and basophilic inclusion body disease are immunoreactive for the fused in sarcoma (FUS) protein, resulting in the creation of a new molecular subgroup (FTLD-FUS), and studies clarifying the functional consequences of pathogenic CHMP2B mutations.

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Authors and Affiliations

  1. Department of Pathology and Laboratory Medicine, University of British Columbia and Vancouver General Hospital, 855 West 12th Avenue, Vancouver, BC, V5Z 1M9, Canada

    Ian R. A. Mackenzie

  2. Institute of Neuropathology, University of Zurich, Zurich, Switzerland

    Manuela Neumann

  3. Department of Pathology and Immunology, Washington University, St. Louis, MO, USA

    Nigel J. Cairns

  4. Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada

    David G. Munoz

  5. Department of Neurodegenerative Disease, UCL Institute of Neurology, London, UK

    Adrian M. Isaacs

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  1. Ian R. A. Mackenzie
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  2. Manuela Neumann
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  3. Nigel J. Cairns
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  4. David G. Munoz
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  5. Adrian M. Isaacs
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Correspondence to Ian R. A. Mackenzie.

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Mackenzie, I.R.A., Neumann, M., Cairns, N.J. et al. Novel Types of Frontotemporal Lobar Degeneration: Beyond Tau and TDP-43. J Mol Neurosci 45, 402–408 (2011). https://doi.org/10.1007/s12031-011-9551-1

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  • DOI: https://doi.org/10.1007/s12031-011-9551-1

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