Kinetic analysis of the polymerization and depolymerization of β2-microglobulin-related amyloid fibrils in vitro

β2-Microglobulin-related (Aβ2M) amyloidosis is a serious complication in patients on long-term dialysis, and partial unfolding of β2-microglobulin (β2-m) is believed to be prerequisite to its assembly into Aβ2M amyloid fibrils. Many kinds of amyloid-associated molecules (e.g., apolipoprotein E (apoE), glycosaminoglycans (GAGs), proteoglycans (PGs)) may contribute to the development of Aβ2M amyloidosis. The formation of Aβ2M 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 Aβ2M amyloid fibrils at a neutral pH, inducing partial unfolding of β2-m and stabilization of the fibrils. Moreover, apoE, GAGs and PGs were found to stabilize Aβ2M 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 β2-m. These findings are consistent with the hypothesis that in vivo, specific molecules that affect the conformation and stability of β2-m and amyloid fibrils will have significant effects on the deposition of Aβ2M amyloid fibrils.