Apolipoprotein E forms stable complexes with recombinant Alzheimer's disease beta-amyloid precursor protein

Apolipoprotein E (apoE), a protein genetically linked to the incidence of Alzheimer's disease, forms SDS-stable complexes in vitro with beta-amyloid peptide (A beta), the primary component of senile plaques. In the present study, we investigated whether apoE was able to bind full-length A beta precursor protein (APP). Using a maltose-binding-protein-APP fusion protein and human very-low-density lipoprotein (VLDL), we detected an interaction of apoE with APP that was inhibited by A beta or anti-apoE antibody. Saturation-binding experiments indicated a single binding equilibrium with an apparent 1:1 stoichiometry and a dissociation constant of 15 nM. An interaction was also observed using apoE from cerebrospinal fluid or delipidated VLDL, as well as recombinant apoE. APP.apoE complexes were SDS-stable, and their formation was not inhibited by reducing conditions; however, they were dissociated by SDS under reducing conditions. ApoE.APP complexes formed high-molecular-mass aggregates, and competition experiments suggested that amino acids 14-23 of A beta are responsible for complex-formation. Finally, no differences were found when studying the interaction of APP with apoE3 or apoE4. Taken together, our results demonstrate that apoE may form stable complexes with the A beta moiety of APP with characteristics similar to those of complexes formed with isolated A beta, and suggest the intriguing possibility that apoE-APP interactions may be pathologically relevant in vivo.