St-Amour Isabelle, Paré Isabelle, Tremblay Cyntia, Coulombe Katherine, Bazin Renée, Calon Frédéric
Centre de Recherche du CHU de Québec, 2705, Boulevard Laurier, Québec, QC G1V 4G2, Canada.
J Neuroinflammation. 2014 Mar 22;11:54. doi: 10.1186/1742-2094-11-54.
Intravenous immunoglobulin (IVIg) is currently in clinical study for Alzheimer's disease (AD). However, preclinical investigations are required to better understand AD-relevant outcomes of IVIg treatment and develop replacement therapies in case of unsustainable supply.
We investigated the effects of IVIg in the 3xTg-AD mouse model, which reproduces both Aβ and tau pathologies. Mice were injected twice weekly with 1.5 g/kg IVIg for 1 or 3 months.
IVIg induced a modest but significant improvement in memory in the novel object recognition test and attenuated anxiety-like behavior in 3xTg-AD mice. We observed a correction of immunologic defects present in 3xTg-AD mice (-22% CD4/CD8 blood ratio; -17% IL-5/IL-10 ratio in the cortex) and a modulation of CX3CR1+ cell population (-13% in the bone marrow). IVIg treatment led to limited effects on tau pathology but resulted in a 22% reduction of the soluble Aβ42/Aβ40 ratio and a 60% decrease in concentrations of 56 kDa Aβ oligomers (Aβ*56).
The memory-enhancing effect of IVIg reported here suggests that Aβ oligomers, effector T cells and the fractalkine pathway are potential pharmacological targets of IVIg in AD.
静脉注射免疫球蛋白（IVIg）目前正处于治疗阿尔茨海默病（AD）的临床研究阶段。然而，需要进行临床前研究以更好地了解IVIg治疗与AD相关的结果，并在供应不可持续的情况下开发替代疗法。
我们在3xTg-AD小鼠模型中研究了IVIg的作用，该模型可重现Aβ和tau病理。小鼠每周注射两次1.5 g/kg IVIg，持续1或3个月。
在新颖物体识别测试中，IVIg诱导3xTg-AD小鼠的记忆力有适度但显著的改善，并减轻了焦虑样行为。我们观察到3xTg-AD小鼠存在的免疫缺陷得到纠正（血液中CD4/CD8比例降低22%；皮质中IL-5/IL-10比例降低17%），并且CX3CR1+细胞群受到调节（骨髓中降低13%）。IVIg治疗对tau病理的影响有限，但可使可溶性Aβ42/Aβ40比例降低22%，56 kDa Aβ寡聚体（Aβ*56）浓度降低60%。
此处报道的IVIg的记忆增强作用表明，Aβ寡聚体、效应T细胞和趋化因子途径是IVIg在AD中的潜在药理学靶点。
