Amyotrophic lateral sclerosis, frontotemporal dementia and beyond: the TDP-43 diseases
- 7 March 2009
- journal article
- review article
- Published by Springer Nature in Zeitschrift für Neurologie
- Vol. 256 (8), 1205-1214
- https://doi.org/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
This publication has 110 references indexed in Scilit:
- Clinical and Pathological Continuum of Multisystem TDP-43 ProteinopathiesArchives of Neurology, 2009
- Amyotrophic Lateral Sclerosis–Plus Syndrome With TAR DNA-Binding Protein-43 PathologyArchives of Neurology, 2009
- TDP-43 in Cerebrospinal Fluid of Patients With Frontotemporal Lobar Degeneration and Amyotrophic Lateral SclerosisArchives of Neurology, 2008
- Two German Kindreds With Familial Amyotrophic Lateral Sclerosis Due to TARDBP MutationsArchives of Neurology, 2008
- Temporal lobar predominance of TDP-43 neuronal cytoplasmic inclusions in Alzheimer diseaseActa Neuropathologica, 2008
- TAR DNA-binding protein-43 in amyotrophic lateral sclerosis, frontotemporal lobar degeneration, and Alzheimer diseaseActa Neuropathologica, 2008
- Phosphorylated TDP‐43 in frontotemporal lobar degeneration and amyotrophic lateral sclerosisAnnals of Neurology, 2008
- TDP-43 protein in plasma may index TDP-43 brain pathology in Alzheimer’s disease and frontotemporal lobar degenerationActa Neuropathologica, 2008
- TDP‐43 A315T mutation in familial motor neuron diseaseAnnals of Neurology, 2008
- TDP‐43 immunoreactivity in hippocampal sclerosis and Alzheimer's diseaseAnnals of Neurology, 2007