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Acta Neuropathologica

, Volume 138, Issue 1, pp 167–169 | Cite as

Revisiting the utility of TDP-43 immunoreactive (TDP-43-ir) pathology to classify FTLD-TDP subtypes

  • Yasushi Nishihira
  • Tamar Gefen
  • Qinwen Mao
  • Christina Appin
  • Missia Kohler
  • Jamie Walker
  • Rosa Rademakers
  • Alfred Rademaker
  • Emily Rogalski
  • Sandra Weintraub
  • Changiz Geula
  • M-Marsel Mesulam
  • Eileen H. BigioEmail author
Correspondence

Until 2006, the term “frontotemporal lobar degeneration with ubiquitinated inclusions (FTLD-U)” referred to a classification system with subtypes based on the distribution of neuronal cytoplasmic inclusions (NCIs), dystrophic neurites (DNs), and neuronal intranuclear inclusions (NIIs), which were immunoreactive to ubiquitin, and tau- and alpha-synuclein negative [1]. In 2006, the 43-kDa TAR DNA-binding protein (TDP-43) was identified as the elemental ubiquitinated protein in FTLD-U, and soon thereafter, the harmonized classification of FTLD-TDP was derived, giving rise to four subtypes (A, B, C, and D) [3, 4]. The term “FTLD-U” was thus replaced with “FTLD-TDP” because cases positive for TDP-43 could be identified based on TDP-43 immunoreactivity (TDP-43-ir). The most obvious challenge to the present FTLD-TDP-based vs. the past FTLD-U-based classification system is that immunohistochemistry for TDP-43 identifies pathologic patterns that are somewhat different from immunohistochemistry...

Notes

References

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    Arai T, Hasegawa M, Akiyama H, Ikeda K, Nonaka T, Mori H et al (2006) TDP-43 is a component of ubiquitin-positive tau-negative inclusions in frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Biochem Biophys Res Commun.  https://doi.org/10.1016/j.bbrc.2006.10.093 CrossRefPubMedGoogle Scholar
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    Mackenzie IR, Neumann M (2017) Reappraisal of TDP-43 pathology in FTLD-U subtypes. Acta Neuropathol 134:79–96.  https://doi.org/10.1007/s00401-017-1716-8 CrossRefPubMedGoogle Scholar
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    Mackenzie IR, Neumann M, Baborie A, Sampathu DM, Du Plessis D, Jaros E et al (2011) A harmonized classification system for FTLD-TDP pathology. Acta Neuropathol 122:111–113.  https://doi.org/10.1007/s00401-011-0845-8 CrossRefPubMedPubMedCentralGoogle Scholar
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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Yasushi Nishihira
    • 1
  • Tamar Gefen
    • 2
    • 3
  • Qinwen Mao
    • 1
    • 3
  • Christina Appin
    • 1
  • Missia Kohler
    • 1
  • Jamie Walker
    • 1
  • Rosa Rademakers
    • 4
  • Alfred Rademaker
    • 3
    • 5
  • Emily Rogalski
    • 2
    • 3
  • Sandra Weintraub
    • 2
    • 3
  • Changiz Geula
    • 3
  • M-Marsel Mesulam
    • 3
    • 6
  • Eileen H. Bigio
    • 1
    • 3
    Email author
  1. 1.Department of PathologyNorthwestern University Feinberg School of MedicineChicagoUSA
  2. 2.Department of Psychiatry and Behavioral SciencesNorthwestern University Feinberg School of MedicineChicagoUSA
  3. 3.Mesulam Center for Cognitive Neurology and Alzheimer’s DiseaseNorthwestern University Feinberg School of MedicineChicagoUSA
  4. 4.Department of NeuroscienceMayo ClinicJacksonvilleUSA
  5. 5.Department of Preventative MedicineNorthwestern University Feinberg School of MedicineChicagoUSA
  6. 6.Department of NeurologyNorthwestern University Feinberg School of MedicineChicagoUSA

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