P2‐057: REMOVAL OF Aβ OLIGOMERS FROM THE BLOOD USING HOLLOW FIBERS: A POTENTIAL THERAPEUTIC SYSTEM FOR ALZHEIMER'S DISEASE

Le résumé fourni par la source

Rapid removal of Aβ from the blood by an extra-corporeal system may act as a peripheral sink from the brain. We have reported that 1) Aβ-monomers can be effectively removed by hemodialyzers, 2) concentrations of blood Aβ-monomers decreased and the influx of Aβ-monomers into the blood were triggered during hemodialysis, 3) hemodialysis patients have fewer Aβ deposition in the brain than controls. Here, we investigated removal of Aβ-oligomers from the blood by hollow fibers and identification of their intact molecular weight in the blood. This study conformed to the Declaration of Helsinki Good Clinical Practice and was approved by the institutional review boards of Fujita Health University and Ogaki Municipal Hospital. The devices used for removal of Aβ-oligomers were plasma component separators membrane-A (sieving coefficient of bovine serum albumin is 0.60) and membrane-B (0.96). In vitro experiment: Human plasma was circulated by dead-end-filtration with membrane-A (n=3) or membrane-B (n=6) for 60 min. Plasma in the pool (Pool), the liquids passed through the membrane walls of the hollow fibers (Pass-through, returned to Pool) and the liquid remained in the hollow fiber lumens (Inside-Lumen) were sampled and analyzed with ELISA for Aβ-oligomers (IBL, Japan). Human study: Blood samples were collected from a patient (52 y, F, renal failure) who received double-filtration-plasmapheresis (DFPP) for 90 min using membrane-A three times (day1,3,6). Plasma separated from blood was introduced plasma component separator, Pass-through was returned to the patient, and Inside-Lumen was discarded (sampled). In vitro experiment: The concentrations of Aβ-oligomers in Pool were effectively reduced by around 80% during 60 min circulation. Almost 90% of Aβ-oligomers were accumulated in Inside-Lumen. Human study: The concentration of Aβ-oligomers in the blood was reduced to almost zero at the end of each DFPP, increased after DFPP, and those at the beginning of DFPP decreased to 1/3 on Day6 compared with Day1. Hollow fiber devices of large appropriate pores effectively removed Aβ-oligomers from the blood. This human study might suggest decrease of Aβ-oligomers in the brain. Acknowledgment: This work was partly supported by KAKENHI (26282126) and Smoking Research Foundation.

Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.