Amyloid ( IF 5.5 ) Pub Date : 2020-12-11 Masayoshi Tasaki, Masamitsu Okada, Akihiro Yanagisawa, Toshiya Nomura, Hiroaki Matsushita, Akihiko Ueda, Yasuteru Inoue, Teruaki Masuda, Yohei Misumi, Taro Yamashita, Takayuki Nakamura, Takeshi Miyamoto, Konen Obayashi, Yukio Ando, Mitsuharu Ueda
Abstract
Amyloidosis is a protein-misfolding disease characterised by insoluble amyloid deposits in the extracellular space of various organs and tissues, such as the brain, heart, kidneys, and ligaments. We previously reported the frequent occurrence of amyloid deposits in the ligament flavum in the presence of lumbar spinal canal stenosis (LSCS), which is a common spinal disorder in older individuals. Our earlier clinicopathological studies revealed that amyloid deposits derived from transthyretin (TTR) were involved in the pathogenesis of LSCS. ATTR amyloid was the most common form in the ligamentum flavum, but amyloid deposits that were not identified still existed in more than 50% of patients with LSCS. In this study, we found apolipoprotein AI (AApoAI) amyloid deposits in the ligamentum flavum of patients with LSCS. The deposits occurred in 12% of patients with LSCS. Biochemical studies revealed that the amyloid deposits consisted mainly of full-length ApoAI. As a notable finding, the lumbar ligamentum flavum of patients who had LSCS with double-positive amyloid deposits—positive for both ATTR and AApoAI—was significantly thicker than that of patients who had LSCS with single-positive—that is, positive for either ATTR or AApoAI—amyloid deposits. We thus suggest that lumbar AApoAI amyloid formation may enhance the pathological changes of lumbar ATTR amyloidosis in patients with LSCS.
中文翻译:
腰椎管狭窄症患者黄韧带中载脂蛋白AI淀粉样蛋白沉积
摘要
淀粉样变性病是一种蛋白质错误折叠的疾病,其特征在于在各种器官和组织(如大脑,心脏,肾脏和韧带)的细胞外空间中存在不可溶的淀粉样蛋白沉积物。我们先前曾报道在存在腰椎管狭窄症(LSCS)的情况下,黄韧带中淀粉样蛋白沉积频繁发生,这是老年人中常见的脊柱疾病。我们较早的临床病理研究表明,源自甲状腺素转运蛋白(TTR)的淀粉样蛋白沉积物参与了LSCS的发病机理。ATTR淀粉样蛋白是黄韧带中最常见的形式,但仍有超过50%的LSCS患者仍存在未鉴定的淀粉样蛋白沉积物。在这项研究中,我们在LSCS患者的黄韧带中发现了载脂蛋白AI(AApoAI)淀粉样蛋白沉积物。沉积物发生在12%的LSCS患者中。生化研究表明,淀粉样蛋白沉积物主要由全长ApoAI组成。一个值得注意的发现是,患有双阳性淀粉样蛋白沉积的LSCS患者(对ATTR和AApoAI都呈阳性)的腰椎黄韧带比具有单阳性LSCS的患者的腰韧带厚得多,也就是说,对ATTR而言都是阳性或AApoAI-淀粉样沉积物。因此,我们建议腰椎AApoAI淀粉样蛋白的形成可能会增强LSCS患者腰椎ATTR淀粉样变性的病理变化。具有双重阳性淀粉样蛋白沉积物(对ATTR和AApoAI均呈阳性)的LSCS患者的腰韧带黄斑明显比具有单一阳性LSCS的患者(即ATTR或AAPOAI)呈淀粉样蛋白沉积的患者的腰椎黄韧带厚。因此,我们建议腰椎AApoAI淀粉样蛋白的形成可能会增强LSCS患者腰椎ATTR淀粉样变性的病理变化。具有双重阳性淀粉样沉积物(对ATTR和AApoAI均呈阳性)的LSCS患者的腰韧带黄斑比具有单一阳性LSCS的患者(即对ATTR或AApoAI)呈淀粉样沉积的患者的腰韧带厚得多。因此,我们建议腰椎AApoAI淀粉样蛋白的形成可能会增强LSCS患者腰椎ATTR淀粉样变性的病理变化。