IJPPP Copyright © 2009-All rights reserved. Published by e-Century Publishing Corporation, Madison, WI 53711
Int J Physiol Pathophysiol Pharmacol 2009;1(1):25-32.

Original Article
Caspase-cleaved TAR DNA-binding protein-43 in Pick’s disease

Troy T. Rohn, Polina Kokoulina

Department of Biology, Science/Nursing Building, Room 228, Boise State University, Boise, Idaho, 83725

Received December 18, 2008; accepted December 22, 2008; available online January 1, 2009

Abstract: The hyperphosphorylation and proteolytic modification of the TAR DNA binding protein-43 (TDP-43) is a key finding in a
number of neurodegenerative diseases including frontotemporal dementia with ubiquitin-positive inclusions (FTLD-U), amyotrophic
lateral sclerosis (ALS), and most recently Alzheimer’s disease (AD). To examine whether proteolytic modifications of TDP-43 is a
relevant finding in Pick’s disease, we utilized a novel site-directed caspase-cleavage antibody based upon a known caspase-3
cleavage consensus site within TDP-43 at position 219. Application of this antibody, termed TDP caspase-cleavage product (TDPccp)
to postmortem Pick’s disease brain sections revealed the presence of caspase-cleaved TDP-43 in Pick and Hirano bodies
predominantly within region CA1 of the hippocampus. Co-localization of TDPccp with PHF-1, a general marker for Pick bodies, as well
as with an antibody to caspase-cleaved tau (TauC3) was evident within the hippocampus. A semi-quantitative analysis indicated that
approximately 21% and 79% of the Pick bodies identified in area CA1 contained caspase-cleaved TDP-43 or caspase-cleaved tau,
respectively. Of interest was the lack of co-localization of TDPccp with PHF-1 in Pick bodies within the dentate gyrus. Collectively, these
data have identified modified TDP-43 as a component of Pick and Hirano bodies that is restricted to area CA1 in Pick’s disease. The
relative paucity of caspase-cleaved TDP-43 found within Pick bodies in comparison to caspase-cleaved tau suggests that TDP-43 and
its modification by caspases is most likely not a contributing factor leading to Pick body formation and evolution. (IJPPP812002).

Key words: Pick’s disease, Pick bodies, Caspases, TDP-43, Hirano Bodies, Tau

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Address all correspondence to:
Troy T. Rohn, PhD
Department of Biology
Science/Nursing Building, Room 228
Boise State University
Boise, Idaho, 83725
Phone number: (208)-426-2396
Fax number: (208-426-4267
E-mail address:
trohn@boisestate.edu