Haruki Koike1, Shohei Ikeda2, Mie Takahashi2, Yuichi Kawagashira2, Masahiro Iijima2, Yohei Misumi2, Yukio Ando2, Shu-Ichi Ikeda2, Masahisa Katsuno2, Gen Sobue1. 1. 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. 2. 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.
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.
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 transthyretinVal30Met 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.