Journal of Neurology

, Volume 256, Issue 8, pp 1205–1214

Amyotrophic lateral sclerosis, frontotemporal dementia and beyond: the TDP-43 diseases

Authors

    • Department of Pathology and Laboratory MedicineUniversity of Pennsylvania School of Medicine
  • Maria Martinez-Lage
    • Department of Pathology and Laboratory MedicineUniversity of Pennsylvania School of Medicine
  • Linda K. Kwong
    • Department of Pathology and Laboratory MedicineUniversity of Pennsylvania School of Medicine
  • Virginia M.-Y. Lee
    • Department of Pathology and Laboratory MedicineUniversity of Pennsylvania School of Medicine
  • John Q. Trojanowski
    • Department of Pathology and Laboratory MedicineUniversity of Pennsylvania School of Medicine
Review

DOI: 10.1007/s00415-009-5069-7

Cite this article as:
Geser, F., Martinez-Lage, M., Kwong, L.K. et al. J Neurol (2009) 256: 1205. doi:10.1007/s00415-009-5069-7

Abstract

Ever since the significance of pathological 43-kDa transactivating responsive sequence DNA-binding protein (TDP-43) for human disease has been recognized in amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration with ubiquitin positive inclusions (FTLD-U), a number of publications have emerged reporting on this pathology in a variety of neurodegenerative diseases. Given the heterogeneous and, in part, conflicting nature of the recent findings, we here review pathological TDP-43 and its relationship to human disease with a special focus on ALS and FTLD-U. To this end, we propose a classification scheme in which pathological TDP-43 is the major disease defining pathology in one group, or is present in addition to other neurodegenerative hallmark pathologies in a second category. We conclude that the TDP-43 proteinopathies represent a novel class of neurodegenerative disorders akin to α-synucleinopathies and tauopathies, with the concept of ALS and FTLD-U to be widened to a broad clinico-pathological multisystem disease, i.e., TDP-43 proteinopathy.

Keywords

Amyotrophic lateral sclerosis (ALS)Frontotemporal dementiaTDP-43 proteinopathy

Copyright information

© Springer-Verlag 2009