Kitaguchi Nobuya, Kawaguchi Kazunori, Sakai Kazuyoshi
Faculty of Clinical Engineering, School of Health Science, Fujita Health University, Toyoake, Japan
Accumulation of amyloid β protein (Aβ) in the brain causes cognitive impairment in Alzheimer’s disease (AD). The nature of the relationship between smoking and AD or dementia has been controversial. However, a recent meta-analysis revealed that smoking is a risk factor for AD. With regard to nicotinic acetylcholinergic receptors (nAChRs), both AD and control patients that smoke have been reported to show an increase in H-cytisine (an α4β4 nAChR agonist) binding in the temporal cortex. The α7 nAChR is also a key factor in AD pathology, particularly in relation to internalization of Aβs. Furthermore, there are many reports showing the neuroprotective effects of nicotine. The internalization of Aβ may lead to Aβ clearance in the brain. We hypothesized that an extracorporeal system that rapidly removes Aβ from the blood may accelerate Aβ clearance from the brain. We have reported that (1) several medical materials including hemodialyzers can effectively remove blood Aβ, (2) the concentrations of blood Aβs decreased during hemodialysis, (3) removal of blood Aβ enhanced Aβ influx into the blood (ideally from the brain), resulting in maintenance or improvement of cognitive function, and (4) Aβ deposition in the brain of hemodialysis patients was significantly lower than in controls. Smoking affected blood Aβ removal efficiencies and brain atrophy. We believe this Extracorporeal Blood Aβ Removal Systems (E-BARS) may contribute as a therapy for AD.
大脑中β淀粉样蛋白（Aβ）的积累会导致阿尔茨海默病（AD）的认知障碍。吸烟与AD或痴呆之间关系的本质一直存在争议。然而，最近的一项荟萃分析表明，吸烟是AD的一个风险因素。关于烟碱型乙酰胆碱能受体（nAChRs），据报道，吸烟的AD患者和对照患者在颞叶皮质中均显示H-野靛碱（一种α4β4 nAChR激动剂）结合增加。α7 nAChR也是AD病理的一个关键因素，特别是与Aβ的内化有关。此外，有许多报告显示尼古丁具有神经保护作用。Aβ的内化可能导致大脑中Aβ的清除。我们假设，一个能快速从血液中清除Aβ的体外系统可能会加速大脑中Aβ的清除。我们已经报道：（1）包括血液透析器在内的几种医用材料可以有效清除血液中的Aβ；（2）血液透析期间血液中Aβ的浓度会降低；（3）清除血液中的Aβ会增强Aβ流入血液（理想情况下是从大脑流入），从而维持或改善认知功能；（4）血液透析患者大脑中的Aβ沉积明显低于对照组。吸烟会影响血液中Aβ的清除效率和脑萎缩。我们认为这种体外血液Aβ清除系统（E-BARS）可能作为一种治疗AD的方法发挥作用。
