**Author Listing - Lead/ Submitting Author (we will be communicating with this individual): Name, Institution, City and State where the work was done. Co-authors will be added in a separate section.**
Rose Pedretti, University of Texas Southwestern Medical Center, Dallas TX

**Main Body of the Abstract**
The aggregation of transthyretin causes ATTR amyloidosis, an incurable condition that can lead to neuropathy and heart failure. ATTR diagnosis requires ruling out many other conditions, leading to diagnostic delays. The development of a blood test to detect ATTR pathology may facilitate early diagnosis, resulting in prognosis improvement. Here we describe the development of a detection probe targeting aggregation-driving segments of transthyretin and ATTR fibrils. We designed our probe through rational design and computational optimization. Using immuno-dot blotting, we validated the binding of our probe to purified ATTR fibrils (A) and aggregates in cardiac tissue homogenates. Our probe detects the presence of previously unknown ATTR aggregates in plasma of ATTR amyloidosis patients (B, orange). These ATTR aggregates are not detected in healthy individuals and light chain amyloidosis patients (C). We also observe a reduction of aggregates in ATTR amyloidosis patients after treatment with gene silencers or tetramer stabilizers (B, blue). These aggregates are observed in individuals carrying ATTR associated mutations before showing symptoms (B, pink). Our data suggest that this biomarker can be exploited to detect aggregated transthyretin in the blood of ATTR amyloidosis patients even prior to showing disease symptoms, and can be used to monitor response to treatment. Our novel probe may represent a revolutionary technology for the detection of ATTR aggregates in plasma and early diagnosis of cardiac ATTR amyloidosis. Early detection of these species may enable earlier treatment, thereby reducing care costs and improving the quality of life of those affected.



Detection of circulating transthyretin amyloid aggregates in plasma: a novel biomarker for transthyretin amyloidosis PB3 (#63)

We invite you to attend the XIX International Symposium on Amyloidosis to be held in Rochester, MN.

This symposium is organized as a hybrid meeting (with the focus on in-person) held from Sunday, May 26 through Thursday, May 30, 2024.

Together with the ISA Board and members of Mayo Clinic, a very attractive scientific hybrid program is being planned. The program will cover a variety of types of systemic amyloidosis: ATTR (hereditary and wild-type), AL (light-chain), AA and less frequent forms. There will be key lectures, specific symposia including those company sponsored, oral presentations and poster sessions of accepted abstracts.

COURSE DESCRIPTION
This program will provide a comprehensive review of state-of-the-art education in systemic amyloidosis: basic science, pathophysiology, diagnosis, current and emerging treatments. Scientific presentations will include competitive oral and poster abstracts. The rapid evolution of scientific discovery and expanding treatment options has created tremendous interest in the field and this meeting will fill and important gap in educating scientists and clinicians.