Pathogenesis of AA amyloidosis

The principal pathogenic factors in AA amyloidosis include overproduction of both HDL-associated and lipid-free SAA in both blood and tissue as a consequence of acute and chronic inflammation. There is proteolytic processing of SAA, mostly SAA1, to AA, with release of the CT third of the molecule; this process involves internalization of SAA by macrophages, intracellular proteolysis, and release of amyloidogenic peptides into the extracellular space. These events are thought to precede fibril formation, but the precise sequence is uncertain. Portions of the peptides have intrinsic fibrillogenic properties.