Acta Neuropathologica

, Volume 118, Issue 2, pp 303–311

TDP-43 pathology in familial British dementia

  • Claudia Schwab
  • Tetsuaki Arai
  • Masato Hasegawa
  • Haruhiko Akiyama
  • Sheng Yu
  • Patrick L. McGeer
Case Report

DOI: 10.1007/s00401-009-0514-3

Cite this article as:
Schwab, C., Arai, T., Hasegawa, M. et al. Acta Neuropathol (2009) 118: 303. doi:10.1007/s00401-009-0514-3

Abstract

Trans-activation-responsive DNA-binding protein 43 (TDP-43) is a component of pathological inclusions in amyotrophic lateral sclerosis and several forms of sporadic and familial frontotemporal lobar degeneration. This has suggested defining a new class of diseases known as TDP-43 proteinopathies. However, it has been reported more recently that TDP-43 positive inclusions occur in other neurodegenerative disorders such as Alzheimer’s disease, Dementia with Lewy Bodies and Parkinsonism dementia complex of Guam. Here we report the occurrence of TDP-43 inclusions in one other neurodegenerative disorder: familial British dementia. Using a variety of antibodies against phosphorylated and non-phosphorylated TDP-43 epitopes, we found intense accumulation occurred in the form of dystrophic neurites, neuronal cytoplasmic inclusions and was also occasionally associated with neurofibrillary tangles. Double immunostaining revealed that TDP-43 and tau aggregates were rarely directly colocalized, but co-existed in the same neurons as separate inclusions. Double staining with ubiquitin showed a direct colocalization with TDP-43. The phosphorylation-dependent TDP-43 antibodies proved superior to phosphorylation-independent antibodies in revealing pathological inclusions since the former did not stain non-phosphorylated TDP-43 in normal nuclei. Our results support the concept that TDP-43 pathology is not narrowly restricted, but is involved in the etiology of many neurodegenerative disorders.

Keywords

TDP-43Familial British dementiaABriUbiquitinIntracellular inclusionsPhosphorylation-dependent TDP-43 antibodies

Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  • Claudia Schwab
    • 1
  • Tetsuaki Arai
    • 2
  • Masato Hasegawa
    • 3
  • Haruhiko Akiyama
    • 2
  • Sheng Yu
    • 1
  • Patrick L. McGeer
    • 1
  1. 1.Department of Psychiatry, Kinsmen Laboratory of Neurological ResearchUniversity of British ColumbiaVancouverCanada
  2. 2.Department of Psychogeriatrics, Tokyo Institute of PsychiatryTokyo Metropolitan Organization for Medical ResearchTokyoJapan
  3. 3.Department of Molecular Neurobiology, Tokyo Institute of PsychiatryTokyo Metropolitan Organization for Medical ResearchTokyoJapan