Serum amyloid a (SAA): biochemistry, genetics and the pathogenesis of AA amyloidosis

Serum amyloid A (apoSAA) is a polymorphic protein encoded by a family of SAA genes in which new members continue to be identi3ed. Those isoforms or allelic forms that are precursors for the amyloidfibril protein A(AA) in reactive (secondary) amyloidosis, are among the acute phase or regulated apoSAA apoproteins complexed with high densig lipoprotein (HDL); other isoforms are expressed constitutively. The chieffunction of apoSAA, which is a well conserved protein found in birds and mammals, has probably not yet been disclosed, but is thought to be part of the host response to infections and tissue damage. Structural and functional aspects of apoSAA. and its role in AA amyloidosis are complex due to the presence of multiple isoforms. Most species appear to possess two main acute phase apoSAA isoforms of hepatic origin in their serum (apoSAA₁ and apoSAA₂ and a third form that has predominant extrahepatic expression (apoSAA₃) A single constitutive isoform, apoSAA₅ has been identijied in human and apoSAA, has been described in BALB/c mice. Thus, apoSAA proteins can be regarded or subclassified as either acute phase reactants (regulated apoSAA also termed A-SAA) or constitutive proteins (C-SAA).