Serum amyloid A amyloid fibrils (AA fibrils)

Serum amyloid A (SAA) amyloid fibrils are insoluble, beta-sheet rich protein aggregates that serve as the pathological hallmark of AA amyloidosis, also known as secondary amyloidosis. These fibrils are formed from the proteolytic cleavage products of Serum Amyloid A, an acute-phase protein synthesized by the liver in response to chronic inflammatory stimuli such as rheumatoid arthritis, Crohn's disease, or familial Mediterranean fever (StatPearls, AA Amyloidosis, 2023). When SAA production is sustained at high levels, the protein misfolds and deposits in the extracellular space of various organs, most critically the kidneys, liver, and spleen, leading to progressive organ dysfunction and failure (PubMed, PMID: 32633432). Therapeutic strategies targeting these fibrils include the use of small molecules like eprodisate, which competitively inhibits the binding of SAA to glycosaminoglycans to prevent fibril polymerization (NEJM, 2007). Additionally, novel approaches involve the depletion of Serum Amyloid P component (SAP) followed by monoclonal antibodies like dezamizumab to trigger the immunological clearance of existing amyloid deposits (NEJM, 2015). Effective management of the target relies heavily on monitoring circulating SAA levels to ensure they remain below the threshold for fibrillogenesis.

Other names

AA amyloidAmyloid A fibrilsSecondary amyloid fibrilsSerum amyloid A protein aggregates

Inhibition of glycosaminoglycan binding to prevent fibril assembly and monoclonal antibody-mediated clearance of amyloid deposits.