Genetic abnormalities and pathogenesis of familial amyloidotic polyneuropathy

Abstract

Familial amyloidotic polyneuropathy (FAP) is an autosomal inherited disease, characterized by extracellular amyloid deposits and by peripheral neuropathy. Amyloid fibrils derived from most types of FAP consist of variant transthyretin (TTR) with single amino acid substitutions, and methionine 30 TTR is the most common variant TTR. TTR is mainly produced in the liver and the choroid plexus. Biochemical and molecular biological techniques have been revealing the amyloidogenicity of variant TTR in vitro and in vivo using the transgenic mouse as a model. It will be important for the development of effective therapy to find out the factors, other than variant TTR, which affect amyloid deposition and define the tissue specificity of amyloid.