Introduction to TTR Amyloidosis

Transthyretin (TTR) is a 127 amino acid, 55 kDa transport protein primarily synthesized in the liver. The protein is a carrier of thyroxine and retinol (vitamin A)-retinol binding protein complex. It is the tertiary carrier of thyroxine in plasma, carrying less T4 than thyroxine-binding globulin (TBG) and albumin. In its native state TTR is a tetramer, i.e. four single chain TTR monomers form a tetrameric complex.

Transthyretin amyloidosis (ATTR) is caused by deposition of TTR amyloid fibrils in various tissues.

The hereditary form of ATTR is caused by autosomal dominant mutations in the TTR gene. The prevailing theory for amyloid formation associated with the amyloidogenic mutations is based on the observations that changes of amino acids are associated with destabilization and dissociation of the TTR tetramer, leading to abnormally folded monomers that ultimately self-assemble to amyloid fibrils (Fig. 1). These TTR amyloid fibrils are then deposited extracellularly in various tissues. There are more than 80 reported TTR single point mutations that have been associated with hereditary ATTR.

FoldRx has published a brochure for doctors of ATTR patients: A Physician’s Guide to Transthyretin Amyloidosis. You may download it direclty from the publications section of our website here or request a hard copy directly from FoldRx or from the Amyloid Research Foundation.