Kitaguchi Nobuya, Kawaguchi Kazunori, Sakata Miwa, Aoki Hiroki, Yamazaki Kazunori, Kaneko Megumi, Kinomura Jun, Kato Masao, Hasegawa Midori, Suzuki Nobuo, Mizuno Masao, Yuzawa Yukio
Faculty of Clinical Engineering, School of Medical Sciences, Fujita Health University, Toyoake, Aichi, 470-1192, Japan.
Department of Nephrology, School of Medicine, Fujita Health University, Toyoake, Aichi, Japan.
Neuropsychiatr Dis Treat. 2021 Jul 13;17:2291-2308. doi: 10.2147/NDT.S317104. eCollection 2021.
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.
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.
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 Aβ influx than that of PSf hemodialyzer alone. However, Aβ 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.
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 Aβ 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.
β淀粉样蛋白（Aβ）是一种引发阿尔茨海默病的脑蛋白。我们已经揭示，体外血液Aβ清除系统会引起大量Aβ流入血液。本研究调查了在引发Aβ流入方面更有效的系统。
在微型柱中比较十六烷基烷基化纤维素珠（HexDC）和聚砜中空纤维片段（PSf - HFs）的Aβ清除活性，以消除过滤效应。然后，将吸附过滤系统应用于PSf血液透析器，以增强Aβ在中空纤维壁微孔上的吸附。分析了肾衰竭患者在单独使用PSf血液透析器治疗8小时或串联连接HexDC和PSf血液透析器治疗4小时期间的血浆Aβ浓度。
在体外研究中，HexDC在60分钟治疗期间的Aβ清除效率约为100%，而PSf - HF片段的清除效率逐渐降低。然而，吸附过滤系统中的PSf血液透析器清除Aβ的效果与HexDC相当或更好。Aβ流入血液的量随时间增加。同时使用HexDC和PSf血液透析器引起的Aβ流入比单独使用PSf血液透析器更大。然而，单独使用PSf血液透析器引起的Aβ流入与联合系统引起的流入相似或略大。在4小时治疗期间，两种系统引起的Aβ流入几乎是正常大脑中估计存在的Aβ的两倍。
单独使用PSf血液透析器较长时间以及同时使用HexDC和PSf血液透析器较短时间可有效引起更大的Aβ流入。仅使用PSf血液透析器就足以引起Aβ流入。这些关于设备和治疗时间的发现可能会为阿尔茨海默病的治疗和预防带来最佳的临床设置。
