Aβ Influx into the Blood Evoked by Different Blood Aβ Removal Systems: A Potential Therapy for Alzheimer's Disease

Amyloid-β (Aβ) is a brain protein that causes Alzheimer's disease. We have revealed that extracorporeal blood Aβ-removal systems evoked a large Aβ influx into the blood. This study investigated the system that is more effective in evoking Aβ influx.

Aβ removal activities were compared between hexadecyl-alkylated cellulose beads (HexDC) and fragments of polysulfone hollow fibers (PSf-HFs) in mini-columns to eliminate the filtration effect. Then, adsorptive filtration systems were adapted for PSf hemodialyzers to enhance Aβ adsorption on micropores in the wall of hollow fibers. Plasma Aβ concentrations of patients with renal failure were analyzed during treatment with PSf hemodialyzers alone for 8 h or tandemly connected HexDC and PSf hemodialyzers for 4 h.

In the in vitro study, Aβ removal efficiency for HexDC was approximately 100% during the 60 min treatment, whereas the removal efficiency for PSf-HF fragments gradually decreased. However, PSf hemodialyzer in adsorptive filtration systems removed Aβs comparably or more than HexDC. Aβ influx into the blood increases time-dependently. Concomitant use of HexDC and PSf hemodialyzer evoked a larger Aβ_1-40 influx than that of PSf hemodialyzer alone. However, Aβ_1-42 influx by PSf hemodialyzer alone was similar to or a little larger than influx by the combined system. Both systems evoked almost doubled Aβ influx than estimated Aβs existing in the normal brain during the 4 h treatment.

PSf hemodialyzer alone for a longer period and concomitant use of HexDC and PSf hemodialyzer for a shorter time effectively evoked a larger Aβ influx. To evoke Aβ_1-42 influx, PSf hemodialyzer alone was effective enough. These findings of devices and treatment time may lead to optimal clinical settings for therapy and prevention of Alzheimer's disease.