RESUMEN
PURPOSE: Amyloid-ß protein (Aß) is one of the causative proteins of Alzheimer's disease. We have been developing extracorporeal blood Aß-removal systems as a method for enhancing Aß clearance from the brain. We reported previously that medical adsorbents and hemodialyzers removed Aß monomers from peripheral blood, which was associated with influx of Aß monomers from the brain into the bloodstream. Our intent here was to develop a method to promote clearance of Aß oligomers and to provide an estimate of the molecular size of intact Aß oligomers in plasma. METHODS: Two hollow-fiber devices with different pore sizes (Membranes A and B) were evaluated as removers of Aß oligomers with human plasma in vitro. The concomitant removal of Aß oligomers and monomers was investigated by using Membrane B and hexadecyl alkylated cellulose beads or polysulfone hemodialyzers. Double-filtration plasmapheresis with Membrane A was investigated as an approach for the removal of plasma Aß oligomers in humans. RESULTS: Aß oligomers were effectively removed by both Membranes A and B. The increase of Aß oligomers in plasma was observed just after the removal of plasma Aß oligomers in humans. The intact molecular size of major Aß oligomers in the plasma was estimated to be larger than albumin at approximately 60 kDa or more. Additionally, the concomitant removal of Aß monomers and oligomers evoked dissociation of larger Aß oligomers into smaller ones and monomers. CONCLUSION: Aß oligomers were cleared from plasma both in vitro and in human subjects by using hollow-fiber membranes with large pores, indicating that their intact sizes were mostly larger than 60 kDa. Aß oligomers in peripheral circulation were increased after some clearances in human. Further investigation will determine whether the Aß oligomers detected in circulation after clearance were via influx from the brain.