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 identified. Those isoforms or allelic forms that are precursors for the amyloid fibril protein A(AA) in reactive (secondary) amyloidosis, are among the acute phase or regulated apoSAA apoproteins complexed with high density lipoprotein (HDL); other isoforms are expressed constitutively. The chief function 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 (apoSAA(1) and apoSAA(2)) and a third form that has predominant extrahepatic expression (apoSAA(3)). A single constitutive isoform, apoSAA(4), has been identified in human and apoSAA(5) 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).