Novel therapeutic approach for Alzheimer's disease by removing amyloid β protein from the brain with an extracorporeal removal system

The accumulation of amyloid beta (Aβ) protein in the brain reflects the cognitive impairment noted in Alzheimer's disease. Recent studies have shown that brain Aβ disappeared and cognitive improvement occurred as a result of passive or active Aβ immunization. Peripheral administration of nonimmunization substances, such as GM1 ganglioside, also reduced brain Aβ. Therefore, we hypothesized that the rapid removal of Aβ from the blood by an extracorporeal system may act as a peripheral Aβ sink from the brain. In the present study, we investigated the Aβ removal activity of medical materials as a first step toward the design of an Aβ removal system. First, the removal activities of six materials were studied for Aβ_1-40 and Aβ_1-42 by batch analysis in albumin solution or in human plasma for 1-16 h. Two of the six materials reduced the Aβ concentrations by 90-99% within 1 h. Next, the two effective materials, hexadecyl-alkylated cellulose particles (HDC) and charcoal, were analyzed in a continuous single-pass system with minicolumns. Both materials showed around 81-90% removal activity for more than 2 h, which corresponded to over 4 l of plasma treatment in humans. In a human extracorporeal system, HDC also removed both Aβ_1-40 and Aβ_1-42 from whole blood circulation. In conclusion, biomedical materials were found that could remove Aβ_1-40 and Aβ_1-42 effectively in an extracorporeal system. It is now conceivable that further studies can be undertaken to reduce Aβ concentrations in the brain to improve cognitive function.