Type I familial amyloid polyneuropathy. A pathological study of the peripheral nervous system.

The neuropathological changes were examined in 2 cases of type I familial amyloid polyneuropathy (FAP), confirmed by a genetic study with human transthyretin (prealbumin) cDNA. These cases were from different foci of type I FAP in Japan, but showed a similar pathology in the peripheral nerves. Loss of dorsal root and sympathetic ganglion neurons, predominantly those of small size, was prominent, whereas ventral horn cells were well preserved. Distally accentuated axonal loss with marked axonal sprouting was the principal feature. Fibre sprouts were ubiquitous throughout the nerves and affected the fibre size distribution. Segmental demyelination and remyelination were prominent in the proximal portions of nerves, but axonal degeneration was more conspicuous in the distal portions. The centrally-directed branches of the primary sensory neurons did not show distally-accentuated axonal loss in the dorsal columns. Amyloid deposits were present universally in the endoneurial spaces of the peripheral nerves, but more prominently in the dorsal root ganglia, sympathetic ganglia and more proximal portions of the nerves, and the distribution correlated well with the occurrence of the pathology of peripheral nerves. Neurofilamentous accumulation was frequent in the proximal axons and neuronal cell bodies of the sensory and sympathetic neurons. Schwann cells and satellite cells to which amyloid deposits were attached frequently showed disappearance of basement membrane and proliferation of distorted processes. The findings in the present cases suggest that the Schwann and satellite cells may be directly affected by the amyloid deposits, but the pathogenetic mechanism of marked axonal and neuronal involvement still remains to be elucidated.