Frontotemporal dementia-associated protein “phosphorylated TDP-43” localizes to atherosclerotic lesions of human carotid and main cerebral arteries

• Takahiko Umahara ^[3] ; Toshiki Uchihara ^[1] ; Kentaro Hirao ^[2] ; Soichiro Shimizu ^[2] ; Takao Hashimoto ^[2] ; Jiro Akimoto ^[2] ; Michihiro Kohno ^[2] ; Haruo Hanyu ^[2]
  1. [1] Nakano General Hospital

     Nakano General Hospital

     Japón

     
  2. [2] Tokyo Medical University

     Tokyo Medical University

     Japón

     
  3. [3] Mizuno Memorial Rehabilitation Hospital, Nishiarai, Adachi-ku, Tokyo, Japan

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• Localización: Histology and histopathology: cellular and molecular biology, ISSN-e 1699-5848, ISSN 0213-3911, Vol. 35, Nº. 2, 2020, págs. 159-167
• Idioma: inglés
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  • 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 colocalization 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 colocalized 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.