Department of Neurology, University Hospital Basel, Basel, Switzerland.
Biol Psychiatry. 2010 Nov 15;68(10):971-4. doi: 10.1016/j.biopsych.2010.01.030. Epub 2010 Mar 31.
Passive immunization for the treatment of Alzheimer's disease (AD) was rapidly translated into clinical trials. However, basic mechanisms of AD immunotherapy remain only partially understood.
We analyzed the dynamic changes of amyloid-β (Aβ) levels in plasma, brain, and cerebrospinal fluid (CSF) as well as cerebral amyloid binding by Aβ antibody after a single β1-antibody infusion into APP(Swedish) and APP(wildtype) transgenic mice at preplaque and plaque-bearing age.
Following intravenous Aβ antibody treatment, plasma Aβ increased rapidly, reaching significantly higher levels in preplaque compared with plaque-bearing mice, whereas cerebral and CSF Aβ remained unchanged. Strikingly, Aβ antibodies exhibited strong cerebral amyloid plaque binding rapidly after intravenous administration in a subset of animals with more severe vascular amyloid.
Rapid plasma Aβ increase after Aβ antibody infusion results primarily from stabilization of Aβ. Nevertheless, the smaller plasma Aβ increase in plaque-bearing mice might be of diagnostic use. Importantly, intravenously administered antibodies can rapidly bind to cerebral plaques, potentially facilitated by vascular-amyloid-mediated damage of the blood-brain barrier.
针对阿尔茨海默病（AD）的被动免疫治疗已迅速转化为临床试验。然而，AD 免疫疗法的基本机制仍知之甚少。
我们分析了 APP（瑞典）和 APP（野生型）转基因小鼠在斑块前和斑块期时单次β1 抗体输注后，血浆、脑和脑脊液（CSF）中的淀粉样蛋白-β（Aβ）水平以及 Aβ 抗体对大脑淀粉样蛋白结合的动态变化。
静脉注射 Aβ 抗体治疗后，血浆 Aβ 迅速增加，在斑块前小鼠中显著高于斑块期小鼠，而脑和 CSF Aβ 保持不变。引人注目的是，在一部分血管淀粉样蛋白病变更严重的动物中，静脉注射后 Aβ 抗体迅速表现出强烈的大脑淀粉样斑块结合。
Aβ 抗体输注后血浆 Aβ 的快速增加主要是由于 Aβ 的稳定。然而，斑块期小鼠中较小的血浆 Aβ 增加可能具有诊断用途。重要的是，静脉内给予的抗体可以快速结合到大脑斑块上，这可能是由血管淀粉样蛋白介导的血脑屏障损伤所促进的。
