Apolipoprotein AI amyloid deposits in the ligamentum flavum in patients with lumbar spinal canal stenosis
Apolipoprotein AI amyloid deposits in the ligamentum flavum in patients with lumbar spinal canal stenosis
复制标题
腰椎管狭窄患者黄韧带中载脂蛋白AI淀粉样蛋白沉积
DOI：
10.1080/13506129.2020.1858404
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发表时间：
2020
期刊：
影响因子：
5.5
通讯作者：
Ueda Mitsuharu
中科院分区：
文献类型：
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作者：
Tasaki Masayoshi;Okada Masamitsu;Yanagisawa Akihiro;Nomura Toshiya;Matsushita Hiroaki;Ueda Akihiko;Inoue Yasuteru;Masuda Teruaki;Misumi Yohei;Yamashita Taro;Nakamura Takayuki;Miyamoto Takeshi;Obayashi Konen;Ando Yukio;Ueda Mitsuharu
淀粉样变性是一种蛋白质错误折叠疾病，其特征在于各种器官和组织（如脑、心脏、肾脏和韧带）的细胞外间隙中的不溶性淀粉样蛋白沉积。我们以前曾报道过腰椎管狭窄症（LSCS）时黄韧带中淀粉样蛋白沉积的频繁发生，这是老年人常见的脊柱疾病。我们早期的临床病理学研究显示，来源于甲状腺素运载蛋白（TTR）的淀粉样蛋白沉积参与了LSCS的发病机制。ATTR淀粉样蛋白是黄韧带中最常见的形式，但在超过50%的LSCS患者中仍然存在未被识别的淀粉样蛋白沉积。在这项研究中，我们发现载脂蛋白AI（AApoAI）淀粉样沉积在黄韧带LSCS患者。12%的LSCS患者发生沉积。生化研究表明，淀粉样蛋白沉积物主要由全长ApoAI组成。作为一个值得注意的发现，LSCS伴双阳性淀粉样蛋白沉积（ATTR和AApoAI均阳性）的患者的腰椎黄韧带明显厚于LSCS伴单阳性（即ATTR或AApoAI淀粉样蛋白沉积阳性）的患者。因此，我们认为腰椎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。
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.