TY - JOUR
T1 - Toward the treatment for Alzheimer’s disease
T2 - adsorption is primary mechanism of removing amyloid β protein with hollow-fiber dialyzers of the suitable materials, polysulfone and polymethyl methacrylate
AU - Kawaguchi, Kazunori
AU - Saigusa, Akira
AU - Yamada, Shinji
AU - Gotoh, Takehiro
AU - Nakai, Shigeru
AU - Hiki, Yoshiyuki
AU - Hasegawa, Midori
AU - Yuzawa, Yukio
AU - Kitaguchi, Nobuya
N1 - Funding Information:
The authors thank Miwa Sakata, Shun Ikedo, Yutaro Matsushita, Tomotaka Seyama, and Hitomi Shima for their technical assistance. This work was partly supported by the Aichi Kidney Foundation, Suzuken Memorial Foundation, KAKENHI (22500419, 22500521 and 26282126) and the Smoking Research Foundation.
Funding Information:
Nobuya Kitaguchi has stock ownership in Asahi Kasei Corporation Co., Ltd. Nobuya Kitaguchi and Kazunori Kawaguchi received research funding from Asahi Kasei Medical Corporation Co., Ltd. The other authors declare that they have no conflict of interest.
Publisher Copyright:
© 2015, The Japanese Society for Artificial Organs.
PY - 2016/6/1
Y1 - 2016/6/1
N2 - 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.
AB - 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.
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U2 - 10.1007/s10047-015-0878-1
DO - 10.1007/s10047-015-0878-1
M3 - Article
C2 - 26686230
AN - SCOPUS:84950237606
VL - 19
SP - 149
EP - 158
JO - Journal of Artificial Organs
JF - Journal of Artificial Organs
SN - 1434-7229
IS - 2
ER -