title: Toward the treatment for Alzheimer's disease: adsorption is primary mechanism of removing amyloid β protein with hollow-fiber dialyzers of the suitable materials, polysulfone and polymethyl methacrylate.
abstract: The accumulation of amyloid β protein (Aβ) in the brain reflects cognitive impairment in Alzheimer's disease. 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. The present study aimed to determine the optimal materials and modality for Aβ removal by hemodialyzers. In a batch analysis, hollow-fiber fragments of polysulfone (PSf) and polymethyl methacrylate (PMMA) showed greater removal efficiency of Aβ than did other materials, such as cellulose-triacetates and ethylene-vinyl alcohol copolymer (PSf:PMMA at 30 min, 98.6 ± 2.4 %:97.8 ± 0.4 % for Aβ1-40 and 96.6 ± 0.3 %:99.0 ± 1.0 % for Aβ1-42). In a modality study, the Aβ solution was applied to PSf dialyzers and circulated in the dialysis and Air-filled adsorption-mode (i.e., the outer space of the hollow fibers was filled with air) or phosphate-buffered saline (PBS)-filled adsorption modes. The Aβ1-40 removal efficiency of the pre/post dialyzer in the Air-filled adsorption-mode was the highest (62.4 ± 12.6 %, p = 0.007). In a flow rate study in the Air-filled adsorption-mode, 200 mL/min showed the highest Aβ1-40 reduction rate of pool solution (97.3 ± 0.8 % at 15 min) compared with 20 mL/min (p = 0.00001) and 50 mL/min (p = 0.00382). PMMA dialyzers showed similar high reduction rates. Thus, the optimal modality for Aβ removal was the adsorption-mode with PSf or PMMA hollow fibers at around 50 mL/min flow rate, which seems to be suitable for clinical use.
authors.affiliation: Faculty of Clinical Engineering, School of Health Science, Fujita Health University, 1-98 Kutsukake-cho, Toyoake, Aichi, 470-1192, Japan. kkawagu@fujita-hu.ac.jp.
authors.forename: Kazunori
authors.initials: K
authors.lastname: Kawaguchi
authors.affiliation: Juntendo University Hospital, Bunkyō, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Saigusa
authors.affiliation: Chukyo Hospital, Nagoya, Japan.
authors.forename: Shinji
authors.initials: S
authors.lastname: Yamada
authors.affiliation: Mie University Hospital, Tsu, Japan.
authors.forename: Takehiro
authors.initials: T
authors.lastname: Gotoh
authors.affiliation: Faculty of Clinical Engineering, School of Health Science, Fujita Health University, 1-98 Kutsukake-cho, Toyoake, Aichi, 470-1192, Japan.
authors.forename: Shigeru
authors.initials: S
authors.lastname: Nakai
authors.affiliation: Faculty of Clinical Engineering, School of Health Science, Fujita Health University, 1-98 Kutsukake-cho, Toyoake, Aichi, 470-1192, Japan.
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Hiki
authors.affiliation: Department of Nephrology, School of Medicine, Fujita Health University, Toyoake, Japan.
authors.forename: Midori
authors.initials: M
authors.lastname: Hasegawa
authors.affiliation: Department of Nephrology, School of Medicine, Fujita Health University, Toyoake, Japan.
authors.forename: Yukio
authors.initials: Y
authors.lastname: Yuzawa
authors.affiliation: Faculty of Clinical Engineering, School of Health Science, Fujita Health University, 1-98 Kutsukake-cho, Toyoake, Aichi, 470-1192, Japan. nkitaguc@fujita-hu.ac.jp.
authors.forename: Nobuya
authors.initials: N
authors.lastname: Kitaguchi
mesh_terms: D000327:Adsorption; D000544:Alzheimer Disease / Q000628:therapy*; D016229:Amyloid beta-Peptides / Q000302:isolation & purification*; D001921:Brain / Q000378:metabolism; D002482:Cellulose / Q000031:analogs & derivatives; D015312:Hemodialysis Solutions; D006464:Hemoperfusion / Q000379:methods*; D006801:Humans; D011108:Polymers; D019904:Polymethyl Methacrylate; D011145:Polyvinyls; D013450:Sulfones
chemical_list: D016229:Amyloid beta-Peptides; D015312:Hemodialysis Solutions; D011108:Polymers; D011145:Polyvinyls; D013450:Sulfones; C020320:ethylene-vinyl alcohol copolymer; C017662:polysulfone P 1700; D002482:Cellulose; D019904:Polymethyl Methacrylate; C024671:cellulose triacetate
keywords: Alzheimer’s disease; Amyloid-β (Aβ); Apheresis; Hemodialysis