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

Apolipoprotein E (apoE) binds to non-fibrillar amyloid beta-peptide with high affinity. We find here that heparin specifically inhibits apoE-amyloid beta-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 beta-peptide. Using thioflavin T assay, we find that heparin promotes fibrillogenesis of amyloid beta-peptide whereas apoE abolishes this effect. The data suggests that the relationship between apoE and glycosaminoglycans may be important for amyloid beta-peptide fibril formation.