Pathology, diagnosis and pathogenesis of AA amyloidosis.

Amyloid is defined as a proteinaceous tissue deposit that shows a typical green birefringence in polarised light after staining with Congo red, the presence of non-branching linear fibrils of indefinite length with an approximate diameter of 10-12 nm and a distinct X-ray diffraction pattern consistent with Pauling's model of a cross-beta fibril. Approximately 45% of generalised amyloidoses are secondary or reactive (AA) amyloidosis. Among the causes of AA amyloidosis are rheumatic diseases, idiopathic diseases, inherited diseases, infectious diseases and malignant tumours. Recent decades have provided significant advances in our understanding of the pathology and pathogenesis of AA amyloidosis. Its pathogenesis is multifactorial involving many variables such as primary structure of the precursor protein, acute phase response, the presence of non-fibril proteins (e.g. amyloid P component, apolipoprotein E, glycosaminoglycans, proteoglycans and basement membrane proteins), receptors, lipid metabolism and proteases. Study of the pathogenesis of AA amyloidosis has provided many insights into the nature of conformational diseases, which may help in the understanding of other members of this particularly heterogeneous group of diseases, such as Alzheimer's disease and transmissible spongiform encephalopathies.