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

Apolipoprotein E (apoE) binds to non-fibrillar amyloid P-peptide with high affinity. We find here that heparin specifically inhibits apoE-amyloid beta -peptide (1-40) interaction. Low molecular weight heparins reduce the affin ity of this interaction 3-fold as it was estimated by surface plasmon reson ance. The binding is not affected by high salt concentration, which prevent s heparin-induced changes of apoE conformation. We propose that rigid prote in conformation, induced by high affinity heparin binding to apoE, is unfav orable for its interaction to amyloid beta-peptide. Using thioflavin T assa y, we find that heparin promotes fibrillogenesis of amyloid beta-peptide wh ereas apoE abolishes this effect. The data suggests that the relationship b etween apoE and glycosaminoglycans may be important for amyloid beta-peptid e fibril formation. (C) 2000 Elsevier Science Ireland Ltd. All rights reser ved.