Profile of beta-amyloid in response to beta-amyloid vacc

在转基因小鼠中，淀粉样蛋白的积累可以通过接种Abeta肽或被动免疫抗Abeta来减少。然而，疫苗接种的作用机制尚不清楚，特别是在至少一个病例中，尽管在这些小鼠中，β肽治疗确实纠正了与淀粉样蛋白积累相关的认知障碍，但并不能有效清除中枢神经系统的淀粉样蛋白。由于目前尚不清楚哪种类型的β是疫苗接种的目标。本研究的第一个目的是检查哪些Abeta物种通过接种疫苗被消除。然后，我将尝试确定疫苗接种引起的抗体的哪个表位对纤维性淀粉样蛋白有反应，而不是弥漫性淀粉样蛋白。Abeta疫苗的概念机制是，诱导的抗Abeta抗体增强了小胶质细胞对Abeta的吞噬，从而从大脑中清除Abeta。然而，我们和其他人的数据表明，外周和中枢神经系统之间的一些相互作用也会影响大脑中Abeta的清除。因此，我将检查β疫苗接种对血浆中β水平的影响。这两项研究将有助于了解Abeta疫苗治疗的分子基础，并为设计用于被动免疫治疗的抗体提供新的策略。基于本研究获得的证据，我将从清除Abeta效率高的小鼠中分离出单克隆抗体，并使用AD模型小鼠测试抗体对记忆障碍的影响。

The accumulation of amyloid in transgenic mice has been reduced by vaccination with either Abeta peptide or passive immunization with anti-Abeta. However, the mechanism by which vaccination works is poorly understood, especially as in at least one case, Abeta peptide administration did not clear CNS amyloid efficiently, even though it did correct cognitive impairment associated with amyloid accumulation in these mice. As it is not clear what type of Abeta is the target for vaccination. The first aim of this study is to examine which Abeta species are eliminated by vaccination. I will then attempt to identify which epitope of antibodies elicited by vaccination respond to fibrillar as opposed to diffuse amyloid. The conceptional mechanism of Abeta vaccination is that elicited anti-Abeta antibodies enhance microglial phagocytosis of Abeta leading to the clearance of Abeta from the brain. However, our, and other's data suggest that some interplay between peripheral and CNS Abeta also influences clearance of Abeta from the brain. Therefore, I will examine the effects of Abeta vaccination on Abeta levels in plasma. These two studies will aid in understanding the molecular basis of Abeta vaccination therapy, and suggest new strategies to design an antibody for passive immunization therapy. Based on evidence to be obtained from this study, I will isolate monoclonal antibodies from the mouse showed high Abeta clearance efficiency, and will test the effects of antibody in memory impairment using AD model mice.