Keywords: The blood-brain barrier (BBB) surrounding the central nervous system (CNS) protects it from widely different potential hazards; Due to its complex structure the pass of compounds across the BBB is highly; restricted; This is an important drawback for the therapy of diseases like brain tumors or Alzheimer´s disease; The high molecular weight drugs used are normally not able to reach its target specifically and in; large amounts; without altering the integrity of the BBB [1]; Many specific transport systems; like LRP1 (Low-density lipoprotein receptor-related protein-1); contribute to the flow of substances between; bloodstream and the CNS. LRP1 has diverse biological functions; including Apolipoprotein E (ApoE) binding and endocytosis; Nanoparticles modified with ApoE; loaded with a drug of interest; could bind to; LRP1. The whole system will be internalized and the drug could pass though the BBB; thereby reaching its target [2]; Previous studies showed the high binding affinity of ApoE to the fourth ligand-binding; domain of LRP1 (LRP1-IV) [3]; In this work; LRP1-IV was expressed on the surface of E. coli using Autodisplay technology; For this purpose an artificial gene for a fusion protein was constructed; The fusion; protein consisted of an N-terminal signal peptide directing the protein across the inner membrane of E. coli; the LRP1-IV domain; and the C-terminal autotransporter facilitating the transport of LRP1-IV to the; surface of the cell; Once LRP1-IV is expressed on the surface; whole cells can be used for binding studies with ApoE; avoiding cumbersome protein purification; [4]; Surface display of LRP1-IV was verified by; western blot of outer membrane preparations and flow cytometry of whole cells with a specific LRP1 antibody; Flow cytometric analysis also indicated that cells displaying LRP1-IV bind purified ApoE3 and; ApoE3 labeled with PromoFluor-NHS 633. Our next step will be to test the binding of ApoE3 modified nanoparticles to surface displayed LRP1-IV. These nanoparticles could be used as carriers across the; BBB for drugs which normally are not able to cross this barrier [5; 6]; The assay established in this study allows further investigation relevant for the development of nanoparticles; since binding affinities; between ApoE3 variants and LRP1-IV or variants thereof could be easily quantified