Expression of the transthyretin gene in Schwann cells and familial amyloidotic polyneuropathy-mediated neurodegeneration

Abstract

Familial amyloidotic polyneuropathy (FAP) is a hereditary systemic amyloidosis, characterized by peripheral neuropathy. Amyloid derived from most types of FAP consists of transthyretin (TTR) variants with single amino-acid substitutions. Patients with FAP typically show early features of sensory polyneuropathy and autonomic neuropathy. Studies have shown that TTR is mainly produced in the liver and choroid plexus, but not in the peripheral nervous system. However, using laser capture microdissection and reverse transcription-polymerase chain reaction, our group recently discovered the expression of the TTR gene in peripheral glial cells of the dorsal root ganglia. However, the source of TTR amyloid deposits may not be restricted to this cell type, as subsequent studies have revealed that the TTR gene is also expressed in Schwann cells of peripheral nerves. Pathological studies on FAP have shown that the neuropathy is primarily axonopathy, despite numerous studies revealing demyelination and Schwann cell abnormalities. TTR amyloid deposits were observed to have a close association with Schwann cells. TTR synthesis in Schwann cells may therefore explain why TTR variants accumulate in the peripheral nervous system in FAP. In this review, we discuss a relationship between expression of the TTR gene in Schwann cells and the pathogenesis of FAP.