Caspase-Cleaved TAR DNA Binding Protein-43 is a Major Pathological Finding in Alzheimer’s Disease
This is an author-produced, peer-reviewed version of this article. The final, definitive version of this document can be found online at Brain Research, published by Elsevier. Copyright restrictions may apply. doi: 10.1016/j.brainres.2008.06.094
The TAR DNA binding protein-43 (TDP-43) has been identified as a major constituent of inclusions found in frontotemporal dementia with ubiquitin-positive inclusions (FTLD-U) and amyotrophic lateral sclerosis (ALS). To determine a possible role for TDP-43 in Alzheimer’s disease (AD), a site-directed caspase-cleavage antibody to TDP-43 based upon a known caspase-3 cleavage consensus site within TDP-43 at position D219 was designed. In vitro, this antibody labeled the predicted 25 kDa caspase-cleavage fragment of TDP-43 without labeling full-length TDP-43 following digestion of recombinant TDP-43 with caspase-3 or treatment of Hela cells with staurosporine. Application of this antibody in postmortem brain sections indicated the presence of caspase-cleaved TDP-43 in Hirano bodies, tangles, reactive astrocytes and neuritic plaques of the AD brain. Caspase-cleaved TDP-43 also co-localized with ubiquitin labeled neurons as well as dystrophic neurites within plaque regions. These results suggest that caspase-cleaved TDP-43 is a major pathological finding in AD and may contribute to the neurodegeneration associated with this disease.
Troy Rohn. "Caspase-Cleaved TAR DNA Binding Protein-43 is a Major Pathological Finding in Alzheimer’s Disease" Brain Research 1228 (2008): 189-198.
Available at: http://works.bepress.com/troy_rohn/1