Disease-Specific Biomarkers in Transthyretin Cardiac Amyloidosis

Curr Heart Fail Rep. 2020 Jun;17(3):77-83. doi: 10.1007/s11897-020-00457-z.


Purpose of review: Transthyretin amyloidosis is an increasingly recognized cause of restrictive cardiomyopathy related to amyloid fibril deposition in cardiac tissues. As treatment therapies have emerged for transthyretin amyloidosis (ATTR), so has interest in using biomarkers to identify disease prior to advanced presentation.

Recent findings: Lower levels of transthyretin and retinol binding protein-4 have been demonstrated in patients with pathogenic mutations of transthyretin either with or without clinical disease. Levels associate with the severity of mutations as well as response to treatment with transthyretin stabilizers or small interfering RNA molecules which silence transthyretin production. Transthyretin stability is the rate limiting step of amyloid fibril formation and directly measuring transthyretin kinetic stability has the potential to identify patients as risk as well as therapeutic response to treatment regardless of pathogenic or wild-type genetics. In addition, non-antibody protein-based peptide probes have been developed that directedly measure misfolded transthyretin oligomers due to transthyretin breakdown. Although promising, both TTR kinetic and protein peptide probes remain in early stages of clinical investigation. Transthyretin, retinol binding protein-4, transthyretin kinetic stability, and protein-based peptide probes have potential as biomarkers to facilitate an earlier ATTR diagnosis for patients with pathogenic transthyretin mutations.

Keywords: Biomarkers; Retinol binding protein; Transthyretin amyloidosis.

Publication types

  • Review

MeSH terms

  • Amyloid Neuropathies, Familial / blood*
  • Amyloid Neuropathies, Familial / genetics
  • Biomarkers / blood
  • Cardiomyopathies / blood*
  • Cardiomyopathies / genetics
  • DNA / genetics*
  • DNA Mutational Analysis
  • Humans
  • Mutation*
  • Prealbumin / genetics
  • Prealbumin / metabolism*


  • Biomarkers
  • Prealbumin
  • DNA

Supplementary concepts

  • Amyloidosis, Hereditary, Transthyretin-Related