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01-06-2016 | Original Article

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

Authors: Kazunori Kawaguchi, Akira Saigusa, Shinji Yamada, Takehiro Gotoh, Shigeru Nakai, Yoshiyuki Hiki, Midori Hasegawa, Yukio Yuzawa, Nobuya Kitaguchi

Published in: Journal of Artificial Organs | Issue 2/2016

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 Aβ_1–40 and 96.6 ± 0.3 %:99.0 ± 1.0 % for Aβ_1–42). 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 Aβ_1–40 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 Aβ_1–40 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.

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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
Authors: Kazunori Kawaguchi
Akira Saigusa
Shinji Yamada
Takehiro Gotoh
Shigeru Nakai
Yoshiyuki Hiki
Midori Hasegawa
Yukio Yuzawa
Nobuya Kitaguchi
Publication date: 01-06-2016
Publisher: Springer Japan
Published in: Journal of Artificial Organs / Issue 2/2016
Print ISSN: 1434-7229
Electronic ISSN: 1619-0904
DOI: https://doi.org/10.1007/s10047-015-0878-1

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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

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