Pan-amyloid deposits

Pan-amyloid deposits are extracellular accumulations of misfolded proteins that form insoluble fibrils characterized by a conserved cross-beta sheet structure [1, 14]. These deposits are the pathological hallmark of over 30 different diseases, collectively known as amyloidosis, including systemic forms like AL and ATTR amyloidosis, as well as localized neurodegenerative conditions like Alzheimer's disease [7, 10, 15]. Unlike therapies that target specific precursor proteins, such as transthyretin stabilizers or light chain suppressors, pan-amyloid targeting focuses on structural motifs or associated components common to all amyloid types [1, 9]. Therapeutic strategies, such as pan-amyloid removal (PAR) antibodies and fusion proteins, aim to opsonize these deposits and recruit the innate immune system, specifically macrophages, to clear existing fibrils from organs and tissues [2, 3, 4]. This approach holds the potential to reverse organ damage and improve clinical outcomes across multiple types and stages of amyloidosis by directly addressing the accumulated toxic burden [5, 7].

Other names

Amyloid fibrilsAmyloid plaquesMisfolded protein aggregatesCross-beta sheet aggregatesSystemic amyloid deposits

Opsonization and macrophage-mediated phagocytosis (ADCP) of amyloid fibrils to facilitate clearance from tissues and organs [2, 3, 4, 15].