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Frontotemporal Lobar Degeneration TDP-43-Immunoreactive Pathological Subtypes: Clinical and Mechanistic Significance

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Frontotemporal Dementias

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1281))

Abstract

Frontotemporal lobar degeneration with TPD-43-immunoreactive pathology (FTLD-TDP) is subclassified based on the type and cortical laminar distribution of neuronal inclusions. The relevance of these pathological subtypes is supported by the presence of relatively specific clinical and genetic correlations. Recent evidence suggests that the different patterns of pathology are a reflection of biochemical differences in the pathological TDP-43 species, each of which is influenced by differing genetic factors. As a result, patient FTLD-TDP subtype may be an important factor to consider when developing biomarkers and targeted therapies for frontotemporal dementia. In this chapter, we first describe the pathological features, clinical and genetic correlations of the currently recognized FTLD-TDP subtypes. We then discuss a number of novel patterns of TDP-43 pathology. Finally, we provide an overview of what is currently known about the biochemical basis of the different FTLD-TDP subtypes and how this may explain the observed phenotypic and pathological heterogeneity.

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Acknowledgments

This work was supported by the NOMIS foundation (MN) and the Canadian Institutes of Health Research (IRM).

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Authors and Affiliations

  1. Department of Neuropathology, University of Tübingen, Tübingen, Germany

    Manuela Neumann

  2. DZNE, German Center for Neurodegenerative Diseases, Tübingen, Germany

    Manuela Neumann

  3. Department of Pathology and Laboratory Medicine, and Center for Neurodegenerative Disease Research, University of Pennsylvania, Philadelphia, PA, USA

    Edward B. Lee

  4. Department of Pathology, University of British Columbia, Vancouver, BC, Canada

    Ian R. Mackenzie

  5. Department of Pathology, Vancouver General Hospital, Vancouver, BC, Canada

    Ian R. Mackenzie

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  1. Manuela Neumann
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  2. Edward B. Lee
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Correspondence to Ian R. Mackenzie .

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Editors and Affiliations

  1. Department of Pathology and Laboratory Medicine, Indiana University, Indianapolis, IN, USA

    Bernardino Ghetti

  2. International Centre for Genetic Engineering and Biotechnology (ICGEB), Trieste, Italy

    Emanuele Buratti

  3. Department of Neurology, Mayo Clinic, Rochester, MN, USA

    Bradley Boeve

  4. VIB Center for Molecular Neurology University of Antwerp-CDE Antwerpen, Belgium, Department of Neuroscience Mayo Clinic Jacksonville, FL, USA, Antwerpen, Belgium

    Rosa Rademakers

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Neumann, M., Lee, E.B., Mackenzie, I.R. (2021). Frontotemporal Lobar Degeneration TDP-43-Immunoreactive Pathological Subtypes: Clinical and Mechanistic Significance. In: Ghetti, B., Buratti, E., Boeve, B., Rademakers, R. (eds) Frontotemporal Dementias . Advances in Experimental Medicine and Biology, vol 1281. Springer, Cham. https://doi.org/10.1007/978-3-030-51140-1_13

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