Bibliographic
This study investigated the effects of IVIg in the 3xTg-AD mouse model, which reproduces both Aβ and tau pathologies. The results show that IVIg treatment ameliorates cognitive performance, decreases Aβ42/Aβ40 ratios and Aβ*56 concentrations in the brain, reduces inflammation, and modulates the expression of CX3CR1 in the bone marrow. These data are consistent with biomarker analyses from the recent phase III trial on IVIg where a dose-dependent decrease in plasmatic Aβ42 and a reduction in PET-determined [18 F] florbetapir binding in the brain were reported. In keeping with the recent failure of anti-Aβ-based immunotherapies to improve cognition in clinical trials, regulation of Aβ pathology may not be sufficient to fully account for the action of IVIg in AD, particularly in the absence of an amelioration of tau pathology and synaptic defects. Thus, a combination of these effects on Aβ pathology and immune parameters is likely responsible for the cognitive improvements detected in IVIg-treated 3xTg- AD mice. More specifically, the present data provides important insights into the mechanism of action of IVIg in AD and identifies Aβ*56 oligomers, effector T cells and fractalkine signaling as possible targets of IVIg.