From Cell Biology to Tissue Engineering


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

Takahiko Umahara1,2,4, Toshiki Uchihara4,5, Kentaro Hirao2, Soichiro Shimizu2, Takao Hashimoto3, Jiro Akimoto3, Michihiro Kohno3 and Haruo Hanyu2

1Department of Neurology, Mizuno Memorial Rehabilitation Hospital, Nisharai, Adachi-ku, Departments of 2Geriatric Medicine and 3Neurosurgery, Tokyo Medical University, Nishishinjuku, Shinjuku-ku, 4Laboratory of Structural Neuropathology, Tokyo Metropolitan Institute of Medical Science and 5Neurology Clinic and Neuromorphomics laboratory, Nitobe-Memorial Nakano General Hospital, Tokyo, Japan

Offprint requests to: Takahiko Umahara, MD, PhD, Department of Neurology, Mizuno Memorial Rehabilitation Hospital, Nisharai, Adachi-ku, Tokyo 123-0848, Japan. e-mail: takami@mizuno.or.jp

Summary. 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. Histol Histopathol 35, 159-167 (2020)

Key words: TDP-43, Vascular smooth muscle cells, Macrophages, Atherosclerosis, Carotid artery, Main cerebral arteries

DOI: 10.14670/HH-18-140