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 aβ 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 aβ42/aβ40 ratio and a 60% decrease in concentrations of 56 kda aβ oligomers (aβ*56).conclusion: 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. © 2014 st-amour et al.; licensee biomed central ltd.