Efficient amyloid A clearance in the absence of immunoglobulins and complement factors

Amyloid A amyloidosis is a protein misfolding disease characterized by deposition of extracellular aggregates derived from the acute-phase reactant serum amyloid A protein. If untreated, amyloid A amyloidosis leads to irreversible damage of various organs, including the kidneys, liver, and heart. Amyloid A deposits regress upon reduction of serum amyloid A concentration, indicating that the amyloid can be efficiently cleared by natural mechanisms. Clearance was proposed to be mediated by humoral immune responses to amyloid. Here, we report that amyloid clearance in mice lacking complement factors 3 and 4 (C3C4^-/-) was equally efficient as in wild-type mice (C57BL/6), and was only slightly delayed in agammaglobulinemic mice (J^H-/-). Hence, antibodies or complement factors are not necessary for natural amyloid clearance, implying the existence of alternative physiological pathways for amyloid removal.