title: Novel therapeutic approach for Alzheimer's disease by removing amyloid beta protein from the brain with an extracorporeal removal system.
abstract: The accumulation of amyloid beta (Abeta) protein in the brain reflects the cognitive impairment noted in Alzheimer's disease. Recent studies have shown that brain Abeta disappeared and cognitive improvement occurred as a result of passive or active Abeta immunization. Peripheral administration of nonimmunization substances, such as GM1 ganglioside, also reduced brain Abeta. Therefore, we hypothesized that the rapid removal of Abeta from the blood by an extracorporeal system may act as a peripheral Abeta sink from the brain. In the present study, we investigated the Abeta removal activity of medical materials as a first step toward the design of an Abeta removal system. First, the removal activities of six materials were studied for Abeta(1-40) and Abeta(1-42) by batch analysis in albumin solution or in human plasma for 1-16 h. Two of the six materials reduced the Abeta 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 Abeta(1-40) and Abeta(1-42) from whole blood circulation. In conclusion, biomedical materials were found that could remove Abeta(1-40) and Abeta(1-42) effectively in an extracorporeal system. It is now conceivable that further studies can be undertaken to reduce Abeta concentrations in the brain to improve cognitive function.
authors.affiliation: Division of Clinical Engineering Technology, Fujita Health University College, Toyoake, Aichi, Japan.
authors.forename: Kazunori
authors.initials: K
authors.lastname: Kawaguchi
authors.forename: Nobuya
authors.initials: N
authors.lastname: Kitaguchi
authors.forename: Shigeru
authors.initials: S
authors.lastname: Nakai
authors.forename: Kazutaka
authors.initials: K
authors.lastname: Murakami
authors.forename: Kunihiko
authors.initials: K
authors.lastname: Asakura
authors.forename: Tatsuro
authors.initials: T
authors.lastname: Mutoh
authors.forename: Yoshiro
authors.initials: Y
authors.lastname: Fujita
authors.forename: Satoshi
authors.initials: S
authors.lastname: Sugiyama
mesh_terms: D000327:Adsorption; D000544:Alzheimer Disease / Q000601:surgery*; D016229:Amyloid beta-Peptides; D005112:Extracorporeal Circulation / Q000379:methods*; D006801:Humans
chemical_list: D016229:Amyloid beta-Peptides