**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.**
Sherry Wong, Boston University Amyloidosis Center, Boston, Massachusetts

**Main Body of the Abstract**
Aggregation of antibody light chain proteins is the hallmark of amyloid light chain (AL) amyloidosis. Patient-derived amyloid fibrils are formed from light chain variable domain residues in non-native conformations. Therefore, light chains must first unfold from their native structures in order to aggregate. We investigated how the processes of unfolding and self-assembly are linked using a well-studied light chain variable domain protein known as WIL, derived from a patient with AL amyloidosis. WIL readily aggregates in vitro under conditions where the native state predominates. Aggregation kinetics, measured using thioflavin T fluorescence, exhibited a lag phase followed by a rapid increase in fluorescence. We measured the effects on aggregation rate from altering protein concentration and adding pre-formed WIL fibril “seeds”. WIL aggregation had a distinctly non-linear dependence on concentration, with a maximum aggregation rate (i.e., a minimum lag phase duration) observed at 8 µM protein concentration. This behavior is consistent with formation of alternate aggregate structures in the early phases of amyloid formation. Addition of N- or C-terminal peptide tags did not greatly affect the folding or stability of the protein, but these tags altered the concentration dependence of aggregation. Aggregation rates increased in the presence of pre-formed seeds, but adding seeds did not eliminate the lag phase even when the proportion of seeds to soluble protein was greater than 1 in 1600. The complexity of aggregation observed in vitro highlights how multiple species may contribute to amyloid pathology in patients.



Kinetic evidence for multiple aggregation pathways in antibody light chain variable domains PA42 (#391)

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.