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.

摘要

淀粉样变性是一种蛋白质错误折叠疾病，其特征是不溶性淀粉样蛋白沉积在各种器官和组织的细胞外空间，例如大脑、心脏、肾脏和韧带。我们之前报道了在存在腰椎管狭窄症 (LSCS) 的情况下，黄韧带中经常出现淀粉样蛋白沉积，这是老年人常见的脊柱疾病。我们早期的临床病理学研究表明，源自转甲状腺素蛋白 (TTR) 的淀粉样蛋白沉积物参与了 LSCS 的发病机制。ATTR 淀粉样蛋白是黄韧带中最常见的形式，但 50% 以上的 LSCS 患者中仍存在未发现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。作为一个值得注意的发现，患有淀粉样蛋白沉积双阳性（ATTR 和 AApoAI 均阳性）的 LSCS 患者的腰椎黄韧带明显厚于单阳性（即 ATTR 阳性）的 LSCS 患者。或 AApoAI——淀粉样蛋白沉积物。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。患有双阳性淀粉样蛋白沉积物（ATTR 和 AApoAI 均呈阳性）的 LSCS 患者的腰椎黄韧带明显比患有单阳性（即 ATTR 或 AApoAI 淀粉样蛋白沉积物阳性）的 LSCS 患者厚. 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。患有双阳性淀粉样蛋白沉积物（ATTR 和 AApoAI 均呈阳性）的 LSCS 患者的腰椎黄韧带明显比患有单阳性（即 ATTR 或 AApoAI 淀粉样蛋白沉积物阳性）的 LSCS 患者厚. 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。