Familial amyloid polyneuropathy: mechanisms leading to nerve degeneration.

Familial amyloid polyneuropathy (FAP) manifests itself as a fiber-length-dependent polyneuropathy predominantly affecting sensory and autonomic nervous systems. Endoneurial amyloid deposits can be noxious to nerve fibers in several ways including mechanical and toxic effects on nerve fibers, and impairment of blood supply. On teased fiber preparations, a mixture of axonal degeneration and a lower proportion of segmental demyelination is observed. Within a few years of the first symptoms there is a near complete disappearance of myelinated and unmyelinated nerve fibers in the nerve samples taken by biopsy. On teased fiber preparations, amyloid deposits induce distortion, demyelination and eventually distal axonal degeneration of neighboring nerve fibers. This "mechanical" effect is associated with a "toxic" effect of amyloid fibrils leading to the disappearance of the basal lamina of Schwann cells, followed by death, presumably by apoptosis. Amyloid deposits often cluster around endoneurial blood vessels, and even invade their wall with subsequent occlusion of endoneurial vessels themselves.