Schwann cell and endothelial cell damage in transthyretin familial amyloid polyneuropathy.

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.