Publication:
Frontotemporal dementia-associated protein "phosphorylated TDP-43" localizes to atherosclerotic lesions of human carotid and main cerebral arteries

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Umahara-35-159-167-2020.pdf(16.91 MB)
Date
2020
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Authors
Umahara, Takahiko ; Uchihara, Toshiki ; Hirao, Kentaro ; Shimizu, Soichiro ; Hashimoto, Takao ; Akimoto, Jiro ; Kohno, Michihiro ; Hanyu, Haruo
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Publisher
Universidad de Murcia, Departamento de Biologia Celular e Histiologia
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DOI
https://doi.org/10.14670/HH-18-140
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info:eu-repo/semantics/article
Description
Abstract
The transactivation response DNA binding protein (TARDP) of 43 kDa (TDP-43) is a nuclear protein pivotal in RNA processing. Because phosphorylated (p) TDP-43 has been identified as a component of ubiquitin-positive and tau-negative inclusions in frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS), it is considered to play a major role in neurodegenerative processes. We investigated the immunolocalization of pTDP-43 in atherosclerotic lesions of human carotid and main cerebral arteries. Furthermore, we investigated the co- localization between pTDP-43 and 14-3-3 eta isoform or high mobility group box 1 (HMGB1). pTDP-43 localized in the cytoplasm of many foamy macrophages located in the periphery of lipid-rich necrotic cores, and in the cytoplasm of infiltrated smooth muscle cell-like cells. pTDP-43 co-localized the 14-3-3 eta isoform in carotid plaques. pTDP-43 also co- localized HMGB1. This is the first demonstration of pTDP-43 immunolocalization in human carotid and main cerebral artery plaques. We believe that demonstration of the localization of pTDP-43 in atherosclerotic lesions is important as this may contribute to the establishment of the clinical diagnostic imaging of FTLD and ALS using the pTDP-43 epitope. Moreover, this finding may be useful for further understanding the role of TDP in cell death.
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TDP-43 , Vascular smooth muscle cells , Macrophages , Atherosclerosis , Carotid artery , Main cerebral arteries
Citation
Histology and Histopathology Vol. 35, nº 2 (2020)
URI
http://hdl.handle.net/10201/125068
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Histology and histopathology Vol.35, nº2 (2020)
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