I. Yamaguchi et al., Apolipoprotein E inhibits the depolymerization of beta 2-microglobulin-related amyloid fibrils at a neutral pH, BIOCHEM, 40(29), 2001, pp. 8499-8507
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.