Format

Send to

Choose Destination
J Neurol. 2009 Aug;256(8):1205-14. doi: 10.1007/s00415-009-5069-7. Epub 2009 Mar 7.

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

Author information

1
Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, HUP, Maloney 3rd Floor, 3600 Spruce Street, Philadelphia, PA 19104-4283, USA. geserfel@mail.med.upenn.edu

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 alpha-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.

PMID:
19271105
PMCID:
PMC2790321
DOI:
10.1007/s00415-009-5069-7
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Springer Icon for PubMed Central
Loading ...
Support Center