**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.**
SIRAC Christophe
Team BioPIC CNRS UMR-7276 INSERM-U1262 Control of the Immune Response B and Lymphoproliferations, Limoges, France

**Main Body of the Abstract**
Despite extensive efforts to decipher the mechanism of fibril formation in AL amyloidosis, the lack of reliable in vivo models hinders the study of the disease in its physiological context. We have developped a transgenic mouse model producing a human AL light chain (LC). Upon induction, the mice develop AL amyloidosis deposits, mainly in heart and vessels.
In the present work, we sought to characterize fibrils, their associated proteins and the effect of soluble LC and AL deposits in hearts of our mouse model. We used histological, proteomic and transcriptomic approaches to analyse cardiac tissue from control, non induced transgenic (amyloid negative) and induced transgenic (amyloid positive) mice.
AL fibrils in mice contain both full length and fragmented LC with a fragmentation pattern highly superposable to that of human AL fibrils from the same LC subgroup (IGLV6-57). We found typical amyloid signature proteins including ApoE, ApoA-IV and vitronectin. Despite the absence of an overt cardiac dysfunction in AL transgenic mice, transcriptomic studies reveal the activation of several typical genes associated to cardiac injury including NPPA, NPPB, LGALS3 or TIMP1 and the induction of pathways already described in vitro by others.
Overall, we confirm that the transgenic AL model closely reproduces human cardiac lesions but also shares with humans the biochemical composition of the deposits. Although not yet symptomatic, typical early impairment of cardiac function is observed in amyloid positive mice. These results confirm the value of the model in helping to better understand the pathophysiology of cardiac AL amyloidosis.



**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.**
SIRAC Christophe
Team BioPIC CNRS UMR-7276 INSERM-U1262 Control of the Immune Response B and Lymphoproliferations, Limoges, France

**Main Body of the Abstract**
Despite extensive efforts to decipher the mechanism of fibril formation in AL amyloidosis, the lack of reliable in vivo models hinders the study of the disease in its physiological context. We have developped a transgenic mouse model producing a human AL light chain (LC). Upon induction, the mice develop AL amyloidosis deposits, mainly in heart and vessels.
In the present work, we sought to characterize fibrils, their associated proteins and the effect of soluble LC and AL deposits in hearts of our mouse model. We used histological, proteomic and transcriptomic approaches to analyse cardiac tissue from control, non induced transgenic (amyloid negative) and induced transgenic (amyloid positive) mice.
AL fibrils in mice contain both full length and fragmented LC with a fragmentation pattern highly superposable to that of human AL fibrils from the same LC subgroup (IGLV6-57). We found typical amyloid signature proteins including ApoE, ApoA-IV and vitronectin. Despite the absence of an overt cardiac dysfunction in AL transgenic mice, transcriptomic studies reveal the activation of several typical genes associated to cardiac injury including NPPA, NPPB, LGALS3 or TIMP1 and the induction of pathways already described _in vitro_ by others.
Overall, we confirm that the transgenic AL model closely reproduces human cardiac lesions but also shares with humans the biochemical composition of the deposits. Although not yet symptomatic, typical early impairment of cardiac function is observed in amyloid positive mice. These results confirm the value of the model in helping to better understand the pathophysiology of cardiac AL amyloidosis.



Characterization of cardiac AL amyloidosis in a transgenic mouse model  PA47 (#522)

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.