TY - JOUR
T1 - Aβ influx into the blood evoked by different blood aβ removal systems
T2 - A potential therapy for alzheimer’s disease
AU - Kitaguchi, Nobuya
AU - Kawaguchi, Kazunori
AU - Sakata, Miwa
AU - Aoki, Hiroki
AU - Yamazaki, Kazunori
AU - Kaneko, Megumi
AU - Kinomura, Jun
AU - Kato, Masao
AU - Hasegawa, Midori
AU - Suzuki, Nobuo
AU - Mizuno, Masao
AU - Yuzawa, Yukio
N1 - Funding Information:
The authors thank Hiroshi Tomizawa of Mizuno Clinic, and, Yuri Sakakibara, Kota Watanabe, Miki Kamiya, and Tatsuya Hama of Fujita Health University for their technical assistance. The authors also thank Yoshiyuki Hiki for fruitful discussion, and Fumiyasu Hirai and Ai Yonezawa of Kaneka for providing HexDC for in vitro experiments. This work was partly supported by KAKENHI (20509008, 23500531, 26282126) and the Smoking Research Foundation.
Funding Information:
Nobuya Kitaguchi has stock ownership in Asahi Kasei Corporation Co., Ltd and reports grants from Japanese Government, grants from Smoking Research Foundation, grants from Asahi Kasei Medical Co. LTD, grants, nonfinancial support from Kaneka Corporation, during the conduct of the study.
Publisher Copyright:
© 2021 Kitaguchi et al.
PY - 2021
Y1 - 2021
N2 - Purpose: Amyloid-β (Aβ) is a brain protein that causes Alzheimer’s disease. We have revealed that extracorporeal blood Aβ-removal systems evoked a large Aβ influx into the blood. This study investigated the system that is more effective in evoking Aβ influx. Methods: Aβ removal activities were compared between hexadecyl-alkylated cellulose beads (HexDC) and fragments of polysulfone hollow fibers (PSf-HFs) in mini-columns to eliminate the filtration effect. Then, adsorptive filtration systems were adapted for PSf hemodialyzers to enhance Aβ adsorption on micropores in the wall of hollow fibers. Plasma Aβ concentrations of patients with renal failure were analyzed during treatment with PSf hemodialyzers alone for 8 h or tandemly connected HexDC and PSf hemodialyzers for 4 h. Results: In the in vitro study, Aβ removal efficiency for HexDC was approximately 100% during the 60 min treatment, whereas the removal efficiency for PSf-HF fragments gradually decreased. However, PSf hemodialyzer in adsorptive filtration systems removed Aβs comparably or more than HexDC. Aβ influx into the blood increases time-dependently. Concomitant use of HexDC and PSf hemodialyzer evoked a larger Aβ1–40 influx than that of PSf hemodialyzer alone. However, Aβ1–42 influx by PSf hemodialyzer alone was similar to or a little larger than influx by the combined system. Both systems evoked almost doubled Aβ influx than estimated Aβs existing in the normal brain during the 4 h treatment. Conclusion: PSf hemodialyzer alone for a longer period and concomitant use of HexDC and PSf hemodialyzer for a shorter time effectively evoked a larger Aβ influx. To evoke Aβ1–42 influx, PSf hemodialyzer alone was effective enough. These findings of devices and treatment time may lead to optimal clinical settings for therapy and prevention of Alzheimer’s disease.
AB - Purpose: Amyloid-β (Aβ) is a brain protein that causes Alzheimer’s disease. We have revealed that extracorporeal blood Aβ-removal systems evoked a large Aβ influx into the blood. This study investigated the system that is more effective in evoking Aβ influx. Methods: Aβ removal activities were compared between hexadecyl-alkylated cellulose beads (HexDC) and fragments of polysulfone hollow fibers (PSf-HFs) in mini-columns to eliminate the filtration effect. Then, adsorptive filtration systems were adapted for PSf hemodialyzers to enhance Aβ adsorption on micropores in the wall of hollow fibers. Plasma Aβ concentrations of patients with renal failure were analyzed during treatment with PSf hemodialyzers alone for 8 h or tandemly connected HexDC and PSf hemodialyzers for 4 h. Results: In the in vitro study, Aβ removal efficiency for HexDC was approximately 100% during the 60 min treatment, whereas the removal efficiency for PSf-HF fragments gradually decreased. However, PSf hemodialyzer in adsorptive filtration systems removed Aβs comparably or more than HexDC. Aβ influx into the blood increases time-dependently. Concomitant use of HexDC and PSf hemodialyzer evoked a larger Aβ1–40 influx than that of PSf hemodialyzer alone. However, Aβ1–42 influx by PSf hemodialyzer alone was similar to or a little larger than influx by the combined system. Both systems evoked almost doubled Aβ influx than estimated Aβs existing in the normal brain during the 4 h treatment. Conclusion: PSf hemodialyzer alone for a longer period and concomitant use of HexDC and PSf hemodialyzer for a shorter time effectively evoked a larger Aβ influx. To evoke Aβ1–42 influx, PSf hemodialyzer alone was effective enough. These findings of devices and treatment time may lead to optimal clinical settings for therapy and prevention of Alzheimer’s disease.
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U2 - 10.2147/NDT.S317104
DO - 10.2147/NDT.S317104
M3 - Article
AN - SCOPUS:85111022145
VL - 17
SP - 2291
EP - 2308
JO - Neuropsychiatric Disease and Treatment
JF - Neuropsychiatric Disease and Treatment
SN - 1176-6328
ER -