In beta(2)-microglobulin-related (A beta(2)M) amyloidosis, a serious complication in patients on long-term dialysis, partial unfolding of beta(2)-microglobulin (beta(2)-M) is believed to be prerequisite to its assembly into A beta(2)M amyloid fibrils. Many kinds of amyloid-associated molecules, (e.g., apolipoprotein E (apoE), glycosaminoglycans (GAGs), proteoglycans (PGs)) may contribute to the development of A beta(2)M amyloidosis. In 1990s, the formation of A beta(2)M amyloid fibrils in vitro was first observed at low pH (2.0-3.0). Very recently, low concentrations of 2,2,2-trifluoroethanol (TFE) and the sub-micellar concentration of sodium dodecyl sulfate, a model for anionic phospholipids, have been reported to cause the extension of A beta(2)M amyloid fibrils at a neutral pH, inducing partial unfolding Of beta(2)-m and stabilization of the fibrils. Moreover, apoE, GAGs, and PGs were found to stabilize A beta(2)M amyloid fibrils at a neutral pH, forming a stable complex with the fibrils. Some GAGs, especially heparin, enhanced the fibril extension in the presence of TFE at a neutral pH. Some PGs, especially biglycan also induced the polymerization of acid-denatured beta(2)-M. These findings are consistent with the hypothesis that in vivo, specific molecules that affect the conformation and stability Of beta(2)-m and amyloid fibrils will have significant effects on the deposition of A beta(2)M amyloid fibrils.