Phosphorylated TDP-43 localizes to
chronic cerebral infarctions in human brains
Takahiko Umahara1,2, Toshiki Uchihara3, Kentaro Hirao2, Soichiro Shimizu2 and Haruo Hanyu2
1Department of Neurology, Mizuno Memorial Rehabilitation Hospital, Nisharai, Adachi-ku, 2Department of Geriatric Medicine, Tokyo Medical University, Nishishinjuku, Shinjuku-ku and 3Neurology Clinic with Neuromorphomics Laboratory, Nitobe-Memorial Nakano General Hospital, Tokyo, Japan
Offprint requests to: Takahiko Umahara, MD, PhD, Department of Neurology, Mizuno Memorial Rehabilitation Hospital, 5-5-5 Nishiarai, Adachi-ku, Tokyo 123-0848, Japan. e-mail: takami@mizuno.or.jp
Summary. 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. Histol Histopathol 35, 1023-1028 (2020)
Key words: TDP-43, Brain infarction, Microglia, Macrophages, 14-3-3 proteins
DOI: 10.14670/HH-18-235