| Summary: | 碩士 === 國立臺灣大學 === 解剖學暨細胞生物學研究所 === 101 === Familial amyloid polyneuropathy (FAP) is characterized by the extracellular deposition of transthyretin (TTR) aggregates which form amyloid fibrils, particularly in the peripheral nervous system. The mechanisms of nerve degeneration in FAP remain unclear. In the present study, we performed morphological and immunohistochemical analysis of sural nerve biopsies from 13 patients with FAP, 3 patients with chronic inflammatory demyelinating polyneuropathy (CIDP), 13 diabetic amputee and 4 control subjects. Although the infiltration pattern of Iba1(+) macrophages resembled that of CIDP, the density of myelinated fibers was markedly reduced in FAP. Narrowing of lumen area (p < 0.05) and thickened wall thickness (p < 0.05) were observed in FAP. In FAP patients, the severity of neuropathy was correlated with capillary wall thickness (p < 0.05) and percentage of lumen area (%) (p < 0.05)。The proportion of fibrin accumulated endoneurial vessels was positively correlated with myelinated fiber density (p < 0.05) and Iba1 expression (p < 0.05). We also examined the expression of tissue factor, thrombomodulin and tissue plasminogen activator (tPA) to investigate the activation of coagulation and fibrinolysis. The immunoreactivity of tissue factor was upregulated in the vessels and associated with fibrin deposition (p < 0.05). But there was no alternation in the thrombomodulin expression. The expression of tPA was almost absent in FAP nerves (p < 0.05). To identify the phenotype of the macrophage present in the endoneurium, immunohistochemistry of CD206 was performed, and it was up-regulated in FAP compared with control group. In conclusion, we provided structural and pathological evidence that vascular changes were related to the severity of nerve degeneration in FAP. Upregulation of coagulation cascade in FAP leading to fibrin deposition in the epineurial and endoneurial vessels was also observed. Moreover, we determined that the macrophage phenotype in the endoneurium which was classified as alternatively activated macrophage, which may offer new insight into the function of macrophages in FAP.
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