Apolipoprotein E inhibits the depolymerization of beta 2-microglobulin-related amyloid fibrils at a neutral pH

beta2-Microglobulin-related (A beta 2M) amyloidosis is a common and serious complication in patients on long-term hemodialysis, and beta2-microglobuli n (beta2-m) is a major structural component of A beta 2M amyloid fibrils. F luorescence spectroscopic analysis with thioflavin T and electron microscop ic study revealed that A beta 2M amyloid fibrils readily depolymerize into monomeric beta2-m at a neutral to basic pH. Circular dichroism analysis rev ealed that soon after the initiation of the depolymerization reaction at pH 7.5, the characteristic spectrum of beta2-m in A beta 2M amyloid fibrils c hanges to resemble that of monomeric beta2-m at pH 7.5. Apolipoprotein E (a poE), a representative amyloid-associated protein, formed a stable complex with A beta 2M amyloid fibrils and inhibited the depolymerization of A beta 2M amyloid fibrils dose-dependently in a range of 0-10 muM. These results showed that apoE could enhance the deposition of amyloid fibrils in vivo, p ossibly by binding directly to the surface of the fibrils and stabilizing t he conformation of beta2-m in the fibrils.