Detection of ATTR aggregates in plasma of polyneuropathic ATTR-V30M amyloidosis patients

Abstract

ATTR amyloidosis is caused by the deposition of transthyretin amyloid fibrils in tissues often leading to organ failure and death. The clinical spectrum of this disease is highly diverse and dependent on many factors including the presence or absence of mutations within the transthyretin protein and/or an individuals ancestry. The phenotypic variability of ATTR amyloidosis makes it difficult to diagnose, delaying treatment and worsening patient prognosis. Our lab has recently developed a peptide probe that detects transthyretin aggregates in plasma of ATTR amyloidosis patients with cardiomyopathy but has not been tested in plasma from polyneuropathic patients. Here we evaluate our probe in a cohort of Portuguese patients carrying the ATTR-V30M mutation and having no cardiac phenotype. We found that we could indeed detect aggregates in their plasma, and there appeared to be no relationship between the presence of aggregates and patient age or gender. Our work has broad implications on the pathobiology of ATTR amyloidosis and contribute to the validation of our probe as a novel detection tool for this disease.