Apolipoprotein E Inhibits the Depolymerization of β2-Microglobulin-Related Amyloid Fibrils at a Neutral pH

Abstract

β2-Microglobulin-related (Aβ2M) amyloidosis is a common and serious complication in patients on long-term hemodialysis, and β2-microglobulin (β2-m) is a major structural component of Aβ2M amyloid fibrils. Fluorescence spectroscopic analysis with thioflavin T and electron microscopic study revealed that Aβ2M amyloid fibrils readily depolymerize into monomeric β2-m at a neutral to basic pH. Circular dichroism analysis revealed that soon after the initiation of the depolymerization reaction at pH 7.5, the characteristic spectrum of β2-m in Aβ2M amyloid fibrils changes to resemble that of monomeric β2-m at pH 7.5. Apolipoprotein E (apoE), a representative amyloid-associated protein, formed a stable complex with Aβ2M amyloid fibrils and inhibited the depolymerization of Aβ2M amyloid fibrils dose-dependently in a range of 0−10 μM. These results showed that apoE could enhance the deposition of amyloid fibrils in vivo, possibly by binding directly to the surface of the fibrils and stabilizing the conformation of β2-m in the fibrils.