Systemic amyloid fibrils (AL, ATTR, and AA types) (Amyloid fibrils)

Systemic amyloid fibrils and deposits are the pathological aggregates responsible for systemic amyloidosis, a group of life-threatening diseases characterized by the extracellular accumulation of misfolded proteins (Merlini & Bellotti, 2003). The primary types include AL (derived from immunoglobulin light chains), ATTR (derived from transthyretin), and AA (derived from serum amyloid A), each involving different precursor proteins but sharing a common cross-beta sheet architecture (Sipe et al., 2016). These fibrils adopt a stable conformation that resists degradation, leading to progressive tissue damage and organ failure, particularly in the heart, kidneys, and nervous system (Benson et al., 2018). Therapeutic strategies targeting these deposits aim to clear existing amyloid through the use of monoclonal antibodies, such as birtamimab and NI006, which recognize misfolded protein conformations (Gertz et al., 2023; Garcia-Pavia et al., 2023). By binding to these fibrils, the antibodies facilitate their removal by the innate immune system, potentially reversing organ dysfunction and improving patient survival.

Other names

Amyloid depositsMisfolded protein aggregatesAmyloid plaques (systemic)Amyloidotic depositsExtracellular amyloid aggregates

Monoclonal antibodies bind to neoepitopes on misfolded proteins or fibrils, promoting macrophage-mediated phagocytosis and clearance of tissue deposits (Gertz et al., 2023; Garcia-Pavia et al., 2023). Small molecules may also disrupt fibril stability or prevent the aggregation of precursor proteins.