Phosphorylated TDP-43 localizes to chronic cerebral infarctions in human brains

• Takahiko Umahara ^[3] ; Toshiki Uchihara ^[1] ; Kentaro Hirao ^[2] ; Soichiro Shimizu ^[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, Nisharai, Adachi-ku

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• Localización: Histology and histopathology: cellular and molecular biology, ISSN-e 1699-5848, ISSN 0213-3911, Vol. 35, Nº. 9, 2020, págs. 1023-1028
• Idioma: inglés
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  • The transactivation response DNA-binding protein of 43 kDa (TDP-43) is a nuclear protein pivotal in RNA processing. Because phosphorylated TDP43 (pTDP-43) has been identified as a component of the ubiquitin-positive and tau-negative inclusions observed in the brains of frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS) patients, it is considered to play a major role in neurodegenerative processes. We previously reported that pTDP-43 is located in macrophages of atherosclerotic lesions of human carotid and major cerebral arteries. We hence hypothesized that pTDP-43 might be localized in the macrophages of other human brain lesions. Therefore, we investigated the immunolocalization of pTDP-43 in human brains with chronic cerebral infarction. Furthermore, we investigated the colocalization of pTDP-43 and the 14-3-3 eta isoform and found that pTDP-43 was localized in many macrophages located in chronic cerebral infarctions, in 6 out of the 15 human brains analyzed. pTDP-43 colocalized with the 14-3-3 eta isoform in these lesions.

    This is the first demonstration of pTDP-43 immunolocalization in chronic cerebral infarctions in human brains. We believe that our findings may be useful towards further understanding the pathophysiological roles of TDP-43 in various neurological disorders.