Key Information
Source
ScienceDirect
Year
2025
summary/abstract
Introduction
Systemic amyloidoses are characterised by the extracellular deposition of unfolded proteins that are converted into insoluble protein fibrils.1 The amyloid substance is defined by its staining properties in terms of binding to Congo Red and the birefringence it adopts when examined under polarised light.2 What defines the different types of amyloidosis is the fibrillar protein precursor, which in the case of transthyretin (TTR) amyloidosis, is a tetrameric protein, which can precipitate to form amyloid deposits in both unmutated (wild type) and mutated variants.
Transthyretin amyloidosis (ATTR) is a very heterogeneous disease that can be associated with multiple clinical manifestations of varying severity and can therefore be considered a systemic disease.3 Although the disease can present with a variety of symptoms, most are related to cardiac or neurological involvement.4 Cardiac manifestations include alterations in diastolic relaxation and the intracardiac conduction system, leading to arrhythmia and heart failure. Neurological involvement causes significant morbidity and is characterised by sensorimotor neuropathy and autonomic neuropathy.3
Given the heterogeneity of presentation and the lack of knowledge about the disease, there is often a significant delay in diagnosis, with patients often consulting with multiple specialists.5, 6 With the emergence of new targeted therapies that are highly effective in the early stages of the disease, early diagnosis is essential to allow the use of treatments that alter the natural course of the disease. Finally, the presence of healthy carriers of pathogenic variants makes their close monitoring very important. All these factors have favoured the development of different biomarkers that are increasingly used in daily clinical practice. Biomarkers can be useful for early diagnosis, for monitoring carriers, for assessing disease progression and risk stratification of patients, and for assessing response to treatment, all aimed at facilitating the adoption of the most appropriate general and specific treatments.
The aim of this article is to review the different existing evidence regarding biomarkers that can be used in ATTR. Given that the predominant clinical manifestations are cardiac and neurological, biomarkers that may be useful in both clinical manifestations will be discussed. Other biomarkers that may be potentially useful in the diagnosis and monitoring of this disease will also be reviewed.