Department of Anatomy and Neurobiology; Zhongshan School of Medicine; Sun Yat-sen University; Guangzhou, PR China.
Hum Vaccin Immunother. 2013 Aug;9(8):1643-53. doi: 10.4161/hv.24830. Epub 2013 May 31.
Immunization with synthetic, preaggregated β-amyloid (Aβ) was the first treatment approach able to dramatically reduce brain Aβ pathology in Alzheimer's disease (AD) animal models. For the development of a safe vaccine, we investigated whether 4Aβ1-15 (four tandem repeats of GPGPG-linked Aβ1-15 sequences) had therapeutic effects in the APP/PS1 transgenic mice model of AD. We described the production of anti-Aβ antibodies in APP/PS1 mice immunized with 4Aβ1-15 mixed with MF59 adjuvant. The anti-Aβ antibody concentrations were increased which bound to AD plaques, markedly reduced Aβ pathology in transgenic AD mice and levels of intracerebral Aβ (soluble and insoluble), whereas increased serum Aβ levels. Immunization via 4Aβ1-15 (mainly of the IgG1 Class) may induce a non-inflammatory Th2 reaction. Immunohistochemistry analysis of MHC Class II and CD45 revealed that microglial cells were in a less activated state. Of note, 4Aβ1-15-immunized mice showed improved acquisition of memory compared with controls in a reference-memory Morris water-maze behavior test. The data identify the novel immunogen 4Aβ1-15 as a promising new tool for AD immunotherapy.
用合成的、预聚集的β-淀粉样蛋白（Aβ）进行免疫接种是第一种能够显著减少阿尔茨海默病（AD）动物模型中大脑 Aβ 病理学的治疗方法。为了开发安全的疫苗，我们研究了 4Aβ1-15（四个串联重复的 GPGPG 连接的 Aβ1-15 序列）在 AD 的 APP/PS1 转基因小鼠模型中是否具有治疗作用。我们描述了用 4Aβ1-15 与 MF59 佐剂混合免疫 APP/PS1 小鼠产生抗 Aβ 抗体的情况。抗 Aβ 抗体浓度增加，与 AD 斑块结合，显著减少转基因 AD 小鼠的 Aβ 病理学和脑内 Aβ（可溶性和不溶性）水平，而血清 Aβ 水平增加。通过 4Aβ1-15（主要是 IgG1 类）免疫接种可能会诱导非炎症性 Th2 反应。MHC Ⅱ类和 CD45 的免疫组织化学分析表明，小胶质细胞处于激活程度较低的状态。值得注意的是，与对照组相比，4Aβ1-15 免疫小鼠在参考记忆 Morris 水迷宫行为测试中表现出记忆获得的改善。这些数据确定了新型免疫原 4Aβ1-15 是 AD 免疫治疗的一种有前途的新工具。
