Haruki Koike1, Ryoji Nishi2, Shohei Ikeda2, Yuichi Kawagashira2, Masahiro Iijima2, Takeo Sakurai3, Takayoshi Shimohata3, Masahisa Katsuno2, Gen Sobue4. 1. Department of Neurology, Nagoya University Graduate School of Medicine, Nagoya, Japan. Electronic address: koike-haruki@med.nagoya-u.ac.jp. 2. Department of Neurology, Nagoya University Graduate School of Medicine, Nagoya, Japan. 3. Department of Neurology and Geriatrics, Gifu University Graduate School of Medicine, Gifu, Japan. 4. Department of Neurology, Nagoya University Graduate School of Medicine, Nagoya, Japan; Research Division of Dementia and Neurodegenerative Disease, Nagoya University Graduate School of Medicine, Nagoya, Japan.. Electronic address: sobueg@med.nagoya-u.ac.jp.
Abstract
INTRODUCTION: We evaluated the morphology of amyloid fibrils in the peripheral nervous system using biopsy or autopsy specimens from hereditary transthyretin amyloidosis patients. The impact of amyloid fibril formation on neighboring tissues was also investigated. METHODS: Sural nerve biopsy specimens from 34 patients were examined using electron microscopy. Twenty-eight patients had Val30Met mutations, and the remaining 6 patients had non-Val30Met mutations (i.e., Glu54Lys, Pro24Ser, Thr49Ala, Val71Ala, Val94Gly, and Ala97Gly). The patients with the Val30Met mutation included a case from Brazil (supposedly of Portuguese origin), 6 early-onset cases from endemic foci in Japan, and 21 late-onset cases from non-endemic areas in Japan. RESULTS: Long amyloid fibers were abundant in the early-onset Val30Met cases from the Japanese endemic foci and Brazil, whereas the amyloid fibrils were generally short in the late-onset Val30Met and non-Val30Met cases. The amyloid fibrils seemed to mature from dotty structures among amorphous electron-dense extracellular materials and pull surrounding tissues during the maturation process. The distortion of Schwann cells close to amyloid fibril masses was conspicuous, particularly in cases with long amyloid fibrils. Atrophy was conspicuous in non-myelinating Schwann cells and bands of Büngner (i.e., Schwann cell subunits that previously contained myelinated axons), particularly those completely surrounded by amyloid fibrils. In contrast, the myelinated fibers tended to be only partially surrounded by amyloid fibrils and morphologically preserved due to their large size. Only a few demyelinated axons were found. CONCLUSION: Pre-fibrillar amyloid precursors appear to play a pivotal role during the initial phase of amyloid fibril formation. The mechanical distortion and subsequent atrophy of Schwann cells resulting from the elongation of amyloid fibrils may be related to small-fiber predominant loss, which is a classical characteristic of amyloid neuropathy. Although rather rare, the destruction of myelin (i.e., demyelination) resulting from amyloid deposition may relate to nerve conduction abnormalities mimicking chronic inflammatory demyelinating polyneuropathy.
INTRODUCTION: We evaluated the morphology of amyloid fibrils in the peripheral nervous system using biopsy or autopsy specimens from hereditary transthyretin amyloidosispatients. The impact of amyloid fibril formation on neighboring tissues was also investigated. METHODS: Sural nerve biopsy specimens from 34 patients were examined using electron microscopy. Twenty-eight patients had Val30Met mutations, and the remaining 6 patients had non-Val30Met mutations (i.e., Glu54Lys, Pro24Ser, Thr49Ala, Val71Ala, Val94Gly, and Ala97Gly). The patients with the Val30Met mutation included a case from Brazil (supposedly of Portuguese origin), 6 early-onset cases from endemic foci in Japan, and 21 late-onset cases from non-endemic areas in Japan. RESULTS: Long amyloid fibers were abundant in the early-onset Val30Met cases from the Japanese endemic foci and Brazil, whereas the amyloid fibrils were generally short in the late-onset Val30Met and non-Val30Met cases. The amyloid fibrils seemed to mature from dotty structures among amorphous electron-dense extracellular materials and pull surrounding tissues during the maturation process. The distortion of Schwann cells close to amyloid fibril masses was conspicuous, particularly in cases with long amyloid fibrils. Atrophy was conspicuous in non-myelinating Schwann cells and bands of Büngner (i.e., Schwann cell subunits that previously contained myelinated axons), particularly those completely surrounded by amyloid fibrils. In contrast, the myelinated fibers tended to be only partially surrounded by amyloid fibrils and morphologically preserved due to their large size. Only a few demyelinated axons were found. CONCLUSION: Pre-fibrillar amyloid precursors appear to play a pivotal role during the initial phase of amyloid fibril formation. The mechanical distortion and subsequent atrophy of Schwann cells resulting from the elongation of amyloid fibrils may be related to small-fiber predominant loss, which is a classical characteristic of amyloid neuropathy. Although rather rare, the destruction of myelin (i.e., demyelination) resulting from amyloid deposition may relate to nerve conduction abnormalities mimicking chronic inflammatory demyelinating polyneuropathy.
Authors: Antonia Carroll; P James Dyck; Mamede de Carvalho; Marina Kennerson; Mary M Reilly; Matthew C Kiernan; Steve Vucic Journal: J Neurol Neurosurg Psychiatry Date: 2022-03-07 Impact factor: 13.654
Authors: Ole Bernt Suhr; Jonas Wixner; Intissar Anan; Hans-Erik Lundgren; Priyantha Wijayatunga; Per Westermark; Elisabet Ihse Journal: PLoS One Date: 2019-02-27 Impact factor: 3.240
Authors: Sheila R Reddy; Eunice Chang; Marian H Tarbox; Michael S Broder; Ryan S Tieu; Spencer Guthrie; Montserrat Vera-Llonch; Michael R Pollock Journal: Neurol Ther Date: 2020-05-25