A potential therapeutic system for Alzheimer's disease using adsorbents with alkyl ligands for removal of blood amyloid β

Amyloid beta proteins (Aβ) in the brain are the main cause of Alzheimer's disease. Peripheral administration of Aβ-binding substances, which may act as a sink for Aβ from the brain, has been reported to reduce brain Aβ. We previously found C16-cellulose beads had high Aβ-removal activity in vitro. In this study, we investigated the optimum surface properties of adsorbents for removal of Aβ in vitro and in humans. Batch analysis was performed with porous cellulose beads or silica beads with or without 2-22 methylene groups. Aβ-removal activity of C16-cellulose beads increased with increasing alkyl chain length. In contrast, with cellulose the amount of Aβ removed by the silica beads decreased with increasing alkyl chain length. Cellulose beads with 16 or 22 methylene groups were best (over 99 % removal) among all the beads tested (p ≤ 0.01). The adsorbent surfaces were analyzed by near-infrared spectroscopy, which revealed that the optimum beads had a sufficiently hydrophobic surface with an appropriate amount of adsorbed water accessible on the surface. Aβ removal efficiency by C16-cellulose beads was investigated for 5 renal failure patients on hemodialysis, resulting in 51.1 ± 6.6 % for Aβ_1-40 and 43.8 ± 4.5 % for Aβ_1-42 (p ≤ 0.01). In conclusion, cellulose beads with 16 or 22 methylene groups and an appropriate amount of adsorbed water were the optimum Aβ adsorbents. The device with C16-cellulose beads had high Aβ removal activity in humans. These adsorbents might be useful for Alzheimer's disease therapy.