May 14, 2008

Evidence of multisystem disorder in whole-brain map of pathological TDP-43 in amyotrophic lateral sclerosis

Archives of Neurology
Felix GeserJohn Q Trojanowski

Abstract

Pathological 43-kDa transactivating responsive sequence DNA-binding protein (TDP-43) has been identified recently as the major disease protein in amyotrophic lateral sclerosis (ALS), and in frontotemporal lobar degeneration with ubiquitinated inclusions, with or without motor neuron disease, but the distribution of TDP-43 pathology in ALS may be more widespread than previously described. To determine the extent of TDP-43 pathology in the central nervous systems of patients with clinically confirmed and autopsy confirmed diagnoses of ALS. Performance of an immunohistochemical whole-central nervous system scan for evidence of pathological TDP-43 in ALS patients. An academic medical center. We included 31 patients with clinically and pathologically confirmed ALS and 8 control participants. Immunohistochemistry and double-labeling immunofluorescence to assess the frequency and severity of TDP-43 pathology. In addition to the stereotypical involvement of upper and lower motor neurons, neuronal and glial TDP-43 pathology was present in multiple areas of the central nervous systems of ALS patients, including in the nigro-striatal system, the neocortical and allocortical areas, and the cerebellum, but not in those of the controls. Thes...Continue Reading

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Mentioned in this Paper

Senile Paranoid Dementia
TARDBP gene
Immunofluorescence Assay
Abnormal Degeneration
Immunohistochemistry
Multisystem Disorder
Ubiquitin
Autopsy
TARDBP
Brain

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