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

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 individual’s 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. ### Competing Interest Statement RP and LS are inventors on a patent application (Provisional Patent Application 63/352,521) submitted by the University of Texas Southwestern Medical Center that covers the composition and structure-based diagnostic methods related to cardiac ATTR amyloidosis. JLG receives honoraria for scientific consulting for Alnylam, Eidos/BridgeBio, Intellia, Pfizer, Alexion, Astra-Zeneca, and Tenax Therapeutics and receives research funding from Pfizer, Eidos/BridgeBio, the Texas Health Resources Clinical Scholars fund, and the NHLBI. AM receives research funding from Pfizer, Ionis/Akcea, Attralus, and Cytokinetics. AM also receives fees from Cytokinetics, BMS, Eidos, Pfizer, Ionis, Lexicon, Alnylam, Attralus, Haya, Intellia, BioMarin, and Tenaya. LS receives honoraria for scientific consulting for Intellia and Attralus, and serves as a member of the advisory board of Alexion.