Acta Neuropathologica

, Volume 118, Issue 2, pp 303–311

TDP-43 pathology in familial British dementia

Authors

  • Claudia Schwab
    • Department of Psychiatry, Kinsmen Laboratory of Neurological ResearchUniversity of British Columbia
  • Tetsuaki Arai
    • Department of Psychogeriatrics, Tokyo Institute of PsychiatryTokyo Metropolitan Organization for Medical Research
  • Masato Hasegawa
    • Department of Molecular Neurobiology, Tokyo Institute of PsychiatryTokyo Metropolitan Organization for Medical Research
  • Haruhiko Akiyama
    • Department of Psychogeriatrics, Tokyo Institute of PsychiatryTokyo Metropolitan Organization for Medical Research
  • Sheng Yu
    • Department of Psychiatry, Kinsmen Laboratory of Neurological ResearchUniversity of British Columbia
    • Department of Psychiatry, Kinsmen Laboratory of Neurological ResearchUniversity of British Columbia
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-43 Familial British dementia ABri Ubiquitin Intracellular inclusions Phosphorylation-dependent TDP-43 antibodies

Copyright information

© Springer-Verlag 2009