transthyretine

Transthyretin, commonly abbreviated TTR and formerly known as prealbumin, is a transport protein in humans. It carries thyroxine (T4) and retinol-binding protein-bound vitamin A between tissues, contributing to thyroid hormone distribution and retinol transport. The protein is mainly synthesized by the liver, with additional production by the choroid plexus of the brain and the retina, and is present in plasma and cerebrospinal fluid.

Structure and function: TTR is a homotetramer composed of four identical subunits, about 14 kDa each. In circulation it can bind two T4 molecules per tetramer. The tetramer can dissociate into monomers, and this dissociation is a key step in the formation of amyloid fibrils that accumulate in transthyretin amyloidosis.

Genetics and disease: Mutations in the TTR gene cause hereditary transthyretin amyloidosis (ATTRv). The most common mutation is Val30Met (V30M). ATTRv can present with neuropathy, cardiomyopathy, or a mixed phenotype. Wild-type transthyretin amyloidosis (ATTRwt) occurs mainly in older adults and is a major cause of senile cardiomyopathy. Diagnosis typically involves genetic testing and confirmation by tissue biopsy with amyloid typing.

Treatment and prognosis: Therapeutic approaches include liver transplantation (historical), TTR stabilizers such as tafamidis and diflunisal to slow tetramer dissociation, and gene-silencing therapies such as patisiran (siRNA) and inotersen (antisense) to reduce hepatic TTR production. Supportive care tailored to organ involvement is essential. Prognosis varies with genotype and extent of organ involvement.

Biomarker context: Serum transthyretin is a negative acute-phase protein; levels decrease with inflammation or malnutrition and can reflect nutritional status, but are not specific for amyloidosis.