title: Schwann cell and endothelial cell damage in transthyretin familial amyloid polyneuropathy.
abstract: OBJECTIVE
  To examine the morphology of Schwann cells and endoneurial microvessels with electron microscopy.
  
  
  METHODS
  Sural nerve biopsy specimens from 49 patients with familial amyloid polyneuropathy (FAP) with transthyretin Val30Met mutation were assessed. Patients included 11 early-onset cases from endemic foci and 38 late-onset cases from nonendemic areas.
  
  
  RESULTS
  Loss of nerve fibers with or without neighboring amyloid deposition was a common feature. The amount of amyloid deposition was greater relative to the extent of nerve fiber loss in early-onset cases than in late-onset cases. The atrophy of Schwann cells, particularly nonmyelinating Schwann cells, that were apposed to amyloid fibrils was more conspicuous in early-onset cases than in late-onset cases. The numbers of endothelial cell nuclei, endothelial cell profiles, and occluded microvessels were significantly increased in the patients with FAP compared with 37 patients with nutritional/alcoholic neuropathies (p < 0.05, 0.01, and 0.01, respectively). Findings suggestive of the disruption of blood-nerve barriers such as the loss of tight junctions and the fenestration of endothelial cells were also found more frequently in the patients with FAP (p < 0.001), regardless of the presence or absence of amyloid deposition.
  
  
  CONCLUSIONS
  These findings suggest that direct insult of amyloid fibrils causes Schwann cell damage, resulting in the predominant loss of small-fiber axons characteristic of early-onset cases. In addition, vasculopathy may participate in the pathogenesis of neuropathy, particularly in late-onset cases.
authors: From the Department of Neurology (H.K., S.I., M.T., Y.K., M.I., M.K., G.S.) and Research Division of Dementia and Neurodegenerative Disease (G.S.), Nagoya University Graduate School of Medicine; Department of Neurology (Y.M., Y.A.), Graduate School of Medical Sciences, Kumamoto University; and Department of Medicine (Neurology and Rheumatology) (S.-i.I.), Shinshu University School of Medicine, Matsumoto, Japan. koike-haruki@med.nagoya-u.ac.jp sobueg@med.nagoya-u.ac.jp.
authors: Haruki
authors: H
authors: Koike
authors: From the Department of Neurology (H.K., S.I., M.T., Y.K., M.I., M.K., G.S.) and Research Division of Dementia and Neurodegenerative Disease (G.S.), Nagoya University Graduate School of Medicine; Department of Neurology (Y.M., Y.A.), Graduate School of Medical Sciences, Kumamoto University; and Department of Medicine (Neurology and Rheumatology) (S.-i.I.), Shinshu University School of Medicine, Matsumoto, Japan.
authors: Shohei
authors: S
authors: Ikeda
authors: From the Department of Neurology (H.K., S.I., M.T., Y.K., M.I., M.K., G.S.) and Research Division of Dementia and Neurodegenerative Disease (G.S.), Nagoya University Graduate School of Medicine; Department of Neurology (Y.M., Y.A.), Graduate School of Medical Sciences, Kumamoto University; and Department of Medicine (Neurology and Rheumatology) (S.-i.I.), Shinshu University School of Medicine, Matsumoto, Japan.
authors: Mie
authors: M
authors: Takahashi
authors: From the Department of Neurology (H.K., S.I., M.T., Y.K., M.I., M.K., G.S.) and Research Division of Dementia and Neurodegenerative Disease (G.S.), Nagoya University Graduate School of Medicine; Department of Neurology (Y.M., Y.A.), Graduate School of Medical Sciences, Kumamoto University; and Department of Medicine (Neurology and Rheumatology) (S.-i.I.), Shinshu University School of Medicine, Matsumoto, Japan.
authors: Yuichi
authors: Y
authors: Kawagashira
authors: From the Department of Neurology (H.K., S.I., M.T., Y.K., M.I., M.K., G.S.) and Research Division of Dementia and Neurodegenerative Disease (G.S.), Nagoya University Graduate School of Medicine; Department of Neurology (Y.M., Y.A.), Graduate School of Medical Sciences, Kumamoto University; and Department of Medicine (Neurology and Rheumatology) (S.-i.I.), Shinshu University School of Medicine, Matsumoto, Japan.
authors: Masahiro
authors: M
authors: Iijima
authors: From the Department of Neurology (H.K., S.I., M.T., Y.K., M.I., M.K., G.S.) and Research Division of Dementia and Neurodegenerative Disease (G.S.), Nagoya University Graduate School of Medicine; Department of Neurology (Y.M., Y.A.), Graduate School of Medical Sciences, Kumamoto University; and Department of Medicine (Neurology and Rheumatology) (S.-i.I.), Shinshu University School of Medicine, Matsumoto, Japan.
authors: Yohei
authors: Y
authors: Misumi
authors: From the Department of Neurology (H.K., S.I., M.T., Y.K., M.I., M.K., G.S.) and Research Division of Dementia and Neurodegenerative Disease (G.S.), Nagoya University Graduate School of Medicine; Department of Neurology (Y.M., Y.A.), Graduate School of Medical Sciences, Kumamoto University; and Department of Medicine (Neurology and Rheumatology) (S.-i.I.), Shinshu University School of Medicine, Matsumoto, Japan.
authors: Yukio
authors: Y
authors: Ando
authors: From the Department of Neurology (H.K., S.I., M.T., Y.K., M.I., M.K., G.S.) and Research Division of Dementia and Neurodegenerative Disease (G.S.), Nagoya University Graduate School of Medicine; Department of Neurology (Y.M., Y.A.), Graduate School of Medical Sciences, Kumamoto University; and Department of Medicine (Neurology and Rheumatology) (S.-i.I.), Shinshu University School of Medicine, Matsumoto, Japan.
authors: Shu-Ichi
authors: SI
authors: Ikeda
authors: From the Department of Neurology (H.K., S.I., M.T., Y.K., M.I., M.K., G.S.) and Research Division of Dementia and Neurodegenerative Disease (G.S.), Nagoya University Graduate School of Medicine; Department of Neurology (Y.M., Y.A.), Graduate School of Medical Sciences, Kumamoto University; and Department of Medicine (Neurology and Rheumatology) (S.-i.I.), Shinshu University School of Medicine, Matsumoto, Japan.
authors: Masahisa
authors: M
authors: Katsuno
authors: From the Department of Neurology (H.K., S.I., M.T., Y.K., M.I., M.K., G.S.) and Research Division of Dementia and Neurodegenerative Disease (G.S.), Nagoya University Graduate School of Medicine; Department of Neurology (Y.M., Y.A.), Graduate School of Medical Sciences, Kumamoto University; and Department of Medicine (Neurology and Rheumatology) (S.-i.I.), Shinshu University School of Medicine, Matsumoto, Japan. koike-haruki@med.nagoya-u.ac.jp sobueg@med.nagoya-u.ac.jp.
authors: Gen
authors: G
authors: Sobue
mesh_terms: D000328:Adult; D000368:Aged; D000682:Amyloid / Q000378:metabolism; D028227:Amyloid Neuropathies, Familial / Q000235:genetics / Q000473:pathology*; D001706:Biopsy; D042783:Endothelial Cells / Q000473:pathology*; D005260:Female; D006801:Humans; D008297:Male; D008854:Microscopy, Electron; D055806:Microvessels / Q000473:pathology*; D008875:Middle Aged; D009154:Mutation; D011228:Prealbumin / Q000235:genetics; D012583:Schwann Cells / Q000473:pathology*; D013497:Sural Nerve / Q000473:pathology*
chemical_list: D000682:Amyloid; D011228:Prealbumin