title: Amyloid deposits derived from transthyretin in the ligamentum flavum as related to lumbar spinal canal stenosis.
abstract: Amyloidosis is a protein conformational disorder with the distinctive feature of extracellular accumulation of amyloid fibrils that come from different proteins. In the ligamentum flavum of the lumbar spine, amyloid deposits were frequently found in elderly patients with lumbar spinal canal stenosis and were at least partially formed by wild-type transthyretin. However, how amyloid deposits in the ligamentum flavum affect lumbar spinal canal stenosis has remained unclear. In this study, we analyzed clinical, pathologic, and radiologic findings of patients with lumbar spinal canal stenosis who had amyloid deposits in the ligamentum flavum. We studied 95 ligamentum flavum specimens obtained from 56 patients with lumbar spinal canal stenosis and 21 ligamentum flavum specimens obtained from 19 patients with lumbar disk herniation. We evaluated histopathologic findings and clinicoradiologic manifestations, such as thickness of the ligamentum flavum and lumbar spinal segmental instability. We found that all 95 ligamentum flavum specimens resected from patients with lumbar spinal canal stenosis had amyloid deposits, which we classified into two types, transthyretin-positive and transthyretin-negative, and that transthyretin amyloid formation in the ligamentum flavum of patients with lumbar spinal canal stenosis was an age-associated phenomenon. The amount of amyloid in the ligamentum flavum was related to clinical manifestations of lumbar spinal canal stenosis, such as thickness of the ligamentum flavum and lumbar spinal segmental instability, in the patients with lumbar spinal canal stenosis with transthyretin-positive amyloid deposits. To our knowledge, this report is the first to show clinicopathologic correlations in transthyretin amyloid deposits of the ligamentum flavum. In conclusion, transthyretin amyloid deposits in the ligamentum flavum may be related to the pathogenesis of lumbar spinal canal stenosis in elderly patients.
authors.affiliation: 1] Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan [2] Department of Neurology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
authors.forename: Akihiro
authors.initials: A
authors.lastname: Yanagisawa
authors.affiliation: Department of Neurology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
authors.forename: Mitsuharu
authors.initials: M
authors.lastname: Ueda
authors.affiliation: Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
authors.forename: Takanao
authors.initials: T
authors.lastname: Sueyoshi
authors.affiliation: Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Okada
authors.affiliation: Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
authors.forename: Toru
authors.initials: T
authors.lastname: Fujimoto
authors.affiliation: Department of Neurology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Ogi
authors.affiliation: Department of Neurology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
authors.forename: Keisuke
authors.initials: K
authors.lastname: Kitagawa
authors.affiliation: Department of Neurology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Tasaki
authors.affiliation: Department of Neurology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
authors.forename: Yohei
authors.initials: Y
authors.lastname: Misumi
authors.affiliation: Department of Neurology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
authors.forename: Toshinori
authors.initials: T
authors.lastname: Oshima
authors.affiliation: 1] Department of Clinical Pharmaceutical Sciences, Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto, Japan [2] Department of Pharmacy, Kumamoto University Hospital, Chuo-ku, Kumamoto, Japan.
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Jono
authors.affiliation: Department of Morphological and Physiological Sciences, Graduate School of Health Sciences, Kumamoto University, Chuo-ku, Kumamoto, Japan.
authors.forename: Konen
authors.initials: K
authors.lastname: Obayashi
authors.affiliation: Kumamoto Orthopaedic Hospital, Chuo-ku, Kumamoto, Japan.
authors.forename: Kei
authors.initials: K
authors.lastname: Hirakawa
authors.affiliation: Kumamoto Orthopaedic Hospital, Chuo-ku, Kumamoto, Japan.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Uchida
authors.affiliation: Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.
authors.forename: Per
authors.initials: P
authors.lastname: Westermark
authors.affiliation: Department of Neurology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
authors.forename: Yukio
authors.initials: Y
authors.lastname: Ando
authors.affiliation: Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Mizuta
mesh_terms: D000368:Aged; D000682:Amyloid / Q000009:adverse effects* / Q000032:analysis; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D017843:Ligamentum Flavum / Q000473:pathology*; D008161:Lumbosacral Region; D008279:Magnetic Resonance Imaging; D008297:Male; D013058:Mass Spectrometry; D011228:Prealbumin / Q000009:adverse effects* / Q000032:analysis; D013130:Spinal Stenosis / Q000209:etiology* / Q000378:metabolism / Q000473:pathology
chemical_list: D000682:Amyloid; D011228:Prealbumin; C041120:amyloid prealbumin