Amyloid A (AA) fibrils (AA fibrils)

Amyloid A (AA) fibrils are insoluble, beta-sheet rich protein aggregates that constitute the pathological hallmark of AA amyloidosis, historically termed secondary amyloidosis (Brunger et al., 2020). These fibrils are formed from the proteolytic cleavage of Serum Amyloid A (SAA), an apolipoprotein and acute-phase reactant produced by the liver during systemic inflammation (UniProt P0DJI8). Chronic inflammatory conditions, such as rheumatoid arthritis, bronchiectasis, or familial Mediterranean fever, result in sustained high plasma concentrations of SAA, which can eventually misfold and deposit as AA fibrils in various organs (Gertz et al., 2020). The kidneys are the most frequently affected site, often leading to nephrotic syndrome and renal failure, though the liver and spleen are also common targets (Real de Asua et al., 2014). Therapeutic approaches focus on reducing the SAA precursor through anti-inflammatory agents, disrupting fibril assembly with glycosaminoglycan mimetics like eprodisate, or targeting the serum amyloid P (SAP) component to trigger immune-mediated clearance of deposits (Bodin et al., 2010). Effective management requires both the control of the underlying inflammatory stimulus and direct intervention against fibril accumulation to prevent irreversible organ damage.

Other names

AA amyloidSerum amyloid A fibrilsSecondary amyloidAmyloid A protein aggregates

Therapeutic strategies include the inhibition of fibril polymerization by mimicking glycosaminoglycans, the depletion of serum amyloid P (SAP) component to destabilize fibrils, and the suppression of precursor serum amyloid A (SAA) protein synthesis through cytokine inhibition (Brunger et al., 2020; Bodin et al., 2010).