IVIg protects the 3xTg-AD mouse model of Alzheimer's disease from memory deficit and Aβ pathology

Background: 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. Methods: We investigated the effects of IVIg in the 3xTg-AD mouse model, which reproduces both A beta and tau pathologies. Mice were injected twice weekly with 1.5 g/kg IVIg for 1 or 3 months. Results: 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 A beta 42/A beta 40 ratio and a 60% decrease in concentrations of 56 kDa A beta oligomers (A beta*56). Conclusion: The memory-enhancing effect of IVIg reported here suggests that A beta oligomers, effector T cells and the fractalkine pathway are potential pharmacological targets of IVIg in AD.