Heparin specifically inhibits binding of apolipoprotein E to amyloid β-peptide

Abstract

Apolipoprotein E (apoE) binds to non-fibrillar amyloid β-peptide with high affinity. We find here that heparin specifically inhibits apoE-amyloid β-peptide (1–40) interaction. Low molecular weight heparins reduce the affinity of this interaction 3-fold as it was estimated by surface plasmon resonance. The binding is not affected by high salt concentration, which prevents heparin-induced changes of apoE conformation. We propose that rigid protein conformation, induced by high affinity heparin binding to apoE, is unfavorable for its interaction to amyloid β-peptide. Using thioflavin T assay, we find that heparin promotes fibrillogenesis of amyloid β-peptide whereas apoE abolishes this effect. The data suggests that the relationship between apoE and glycosaminoglycans may be important for amyloid β-peptide fibril formation.