**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.**
Rebecca Price, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool.

**Main Body of the Abstract**
Compositional changes in the gut microbiome, frequently observed in amyloid diseases, can induce chronic inflammation and increased gut barrier permeability. This altered composition is known to modulate communication between the gut and the brain. Within the gut microbiome, both as common inhabitants and pathogens, are species that produce functional amyloids. Rather than arising as a misfolding, functional amyloids have evolved to produce amyloid structures. Bacterial functional amyloids exploit the structural properties of amyloid to aid in biofilm formation. A proposed mechanism behind this process is cross-seeding, where preformed fibrils from one amyloid protein template the misfolding of another monomeric amyloid protein.
Here we investigate the ability of both FapC and CsgA, the major components of Fap and curli fibres respectively, to cross-seed amyloid-β, α-synuclein and Medin. We assess alterations in aggregation kinetics by ThT assay, fibril morphology in both seeded and non-seeded conditions by transmission electron microscopy (TEM) and assess secondary structure changes by fourier transform infrared spectroscopy (FT-IR). Additionally, we assess their associated cell toxicity across neuronal and epithelial cells.
We show that FapC and CsgA can alter the aggregation kinetics and fibril morphology of amyloid-β and medin in vitro. We report that cross-seeded fibrils show distinct secondary structure by FT-IR. Additionally, we observe altered cell toxicity for cross-seeded amyloids along with cell-type dependent toxicity of functional amyloid proteins. This data contributes to understanding how functional amyloids could influence amyloid disease and also provides insights into cross-seeding as a mechanism for disease initiation and progression.



**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.**
Rebecca Price, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool.

**Main Body of the Abstract**
Compositional changes in the gut microbiome, frequently observed in amyloid diseases, can induce chronic inflammation and increased gut barrier permeability. This altered composition is known to modulate communication between the gut and the brain. Within the gut microbiome, both as common inhabitants and pathogens, are species that produce functional amyloids. Rather than arising as a misfolding, functional amyloids have evolved to produce amyloid structures. Bacterial functional amyloids exploit the structural properties of amyloid to aid in biofilm formation. A proposed mechanism behind this process is cross-seeding, where preformed fibrils from one amyloid protein template the misfolding of another monomeric amyloid protein.
Here we investigate the ability of both FapC and CsgA, the major components of Fap and curli fibres respectively, to cross-seed amyloid-β, α-synuclein and Medin. We assess alterations in aggregation kinetics by ThT assay, fibril morphology in both seeded and non-seeded conditions by transmission electron microscopy (TEM) and assess secondary structure changes by fourier transform infrared spectroscopy (FT-IR). Additionally, we assess their associated cell toxicity across neuronal and epithelial cells.
We show that FapC and CsgA can alter the aggregation kinetics and fibril morphology of amyloid-β and medin _in vitro_. We report that cross-seeded fibrils show distinct secondary structure by FT-IR. Additionally, we observe altered cell toxicity for cross-seeded amyloids along with cell-type dependent toxicity of functional amyloid proteins. This data contributes to understanding how functional amyloids could influence amyloid disease and also provides insights into cross-seeding as a mechanism for disease initiation and progression.



Investigating cross-seeding interactions of functional amyloids OC19 (#350)

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.