Plasma Transthyretin and Its Ligands

Transthyretin (TTR) is a homotetrameric protein mainly synthesized by the liver and the choroid plexus whose function is to carry the thyroid hormone thyroxine (t4) and the retinol/retinol-binding protein 4 (holo-RBP4) complexes in plasma and cerebrospinal fluid. The disruption of the TTR tetrameric structure is the permissive step for the formation and deposition of insoluble amyloid fibrils within extracellular matrix of tissues, especially cardiac and nervous tissue. Transthyretin amyloidosis (ATTR) is a progressive disorder whose diagnosis and follow-up are based on clinical, imaging, and laboratory signs of organ involvement. Regarding ATTR, laboratory biomarkers include those of organ damage but not the TTR itself or its ligands. The aim of this chapter is to present the current knowledge on circulating TTR and the laboratory methods available for its quantification and identification of genetic variants. Furthermore, the influence of T4 and holoRBP4 on TTR structural stability will be discussed. Further studies are needed to understand whether and to what extent T4 and holoRPB4 can influence the course of wild-type or variant ATTR.