TDP-43 in the hypoglossal nucleus identifies amyotrophic lateral sclerosis in behavioral variant frontotemporal dementia

Glenda M. Halliday, Matthew C. Kiernan, Jillian J. Kril, Remika Mito, Masami Masuda-Suzukake, Masato Hasegawa, Heather McCann, Lauren Bartley, Carol Dobson-Stone, John B.J. Kwok, Michael Hornberger, John R. Hodges, Rachel H. Tan

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Abstract

The hypoglossal nucleus was recently identified as a key brain region in which the presence of TDP-43 pathology could accurately discriminate TDP-43 proteinopathy cases with clinical amyotrophic lateral sclerosis (ALS). The objective of the present study was to assess the hypoglossal nucleus in behavioral variant frontotemporal dementia (bvFTD), and determine whether TDP-43 in this region is associated with clinical ALS. Twenty-nine cases with neuropathological FTLD-TDP and clinical bvFTD that had not been previously assessed for hypoglossal TDP-43 pathology were included in this study. Of these 29 cases, 41% (n = 12) had a dual diagnosis of bvFTD-ALS at presentation, all 100% (n = 12) of which demonstrated hypoglossal TDP-43 pathology. Of the 59% (n = 17) cohort that presented with pure bvFTD, 35% (n = 6) were identified with hypoglossal TDP-43 pathology. Review of the case files of all pure bvFTD cases revealed evidence of possible or probable ALS in 5 of the 6 hypoglossal-positive cases (83%) towards the end of disease, and this was absent from all cases without such pathology. In conclusion, the present study validates grading the presence of TDP-43 in the hypoglossal nucleus for the pathological identification of bvFTD cases with clinical ALS, and extends this to include the identification of cases with possible ALS at end-stage.
Original languageEnglish
Pages (from-to)197-201
Number of pages5
JournalJournal of the Neurological Sciences
Volume366
Early online date4 May 2016
DOIs
Publication statusPublished - 15 Jul 2016

Keywords

  • Amyotrophic lateral sclerosis
  • Behavioral variant frontotemporal dementia
  • TDP-43
  • Hypoglossal nucleus

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