Spatial patterns of phosphorylation-dependent TDP-43-immunoreactive neuronal cytoplasmic inclusions (NCI) in frontotemporal lobar degeneration with TDP-43 proteinopathy (FTLD-TDP)


The transactive response (TAR) DNA-binding protein of 43kDa (TDP-43) is an RNA binding protein encoded by the TARDPB gene. Abnormal aggregations of TDP-43 in neurons in the form of neuronal cytoplasmic inclusions (NCI) are the pathological hallmark of frontotemporal lobar degeneration with TDP-43 proteinopathy (FTLD-TDP). To investigate the role of TDP-43 in FTLD-TDP, the spatial patterns of the NCI were studied in frontal and temporal cortex of FTLD-TDP cases using a phosphorylation dependent anti-TDP-43 antibody (pTDP-43). In many regions, the NCI formed clusters and the clusters were distributed regularly parallel to the tissue boundary. In about 35% of cortical regions, cluster size of the NCI was within the size range of the modular columns of the cortex. The spatial patterns of the pTDP-immunoreactive inclusions were similar to those revealed by a phosphorylation-independent anti-TDP-43 antibody and also similar to inclusions characterized by other molecular pathologies such as tau, ?-synuclein and ‘fused in sarcoma’ (FUS). In conclusion, the data suggest degeneration of cortical and hippocampal anatomical pathways associated with accumulation of cellular pTDP-43 is characteristic of FTLD-TDP. In addition, the data are consistent with the hypothesis of cell to cell transfer of pTDP-43 within the brain.

Divisions: College of Health & Life Sciences > School of Optometry > Optometry
College of Health & Life Sciences > School of Optometry > Optometry & Vision Science Research Group (OVSRG)
College of Health & Life Sciences
College of Health & Life Sciences > School of Optometry > Vision, Hearing and Language
College of Health & Life Sciences > Clinical and Systems Neuroscience
Additional Information: © The Author(s) 2013. Published by Lorem Ipsum Press. Creative Commons Attribution License
Uncontrolled Keywords: frontotemporal lobar degeneration,TDP-43 proteinopathy,neuronal cytoplasmic inclusions,spatial pattern,FTLD-TDP,transactive response TAR DNA-binding protein of 43 kDa,NCI
Publication ISSN: 2241-0090
Last Modified: 01 Mar 2024 08:09
Date Deposited: 29 Nov 2013 12:42
Full Text Link: http://www.jmol ... rticle/view/105
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PURE Output Type: Article
Published Date: 2013-01-17
Published Online Date: 2013-01-17
Authors: Armstrong, Richard (ORCID Profile 0000-0002-5046-3199)



Version: Published Version

License: Creative Commons Attribution

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