Biodistribution of IVIg after systemic injections: absence of specific immune response. Concentrations of human IgG were evaluated in the (A) plasma, (B) parietotemporal cortex and (C) splenocytes of NonTg and 3xTgAD mice after a 3-month treatment with IVIg (1.5 g/kg) or vehicle. The concentrations of IVIg were measured in plasma and parietotemporal homogenates from intracardially-perfused 16-month-old mice, using a specific ELISA. MFI quantification of extracellular human IgG on CD45+ splenocytes was used to determine the presence of IVIg in splenocytes of 12-month-old mice. Note that the MFI of the control groups was equivalent to the isotypic control and autofluorescence. Data are presented as the mean ± SEM of 7 to 8 NonTg and 11 to 13 3xTg-AD animals. One-way ANOVA followed by Tukey’s multiple comparison test. ***P <0.001 versus control groups. (D) Repeated injections of IVIg did not induce a significant anti-human-specific immune response as shown with human-specific ELISPOT results. Data are presented as the percentage of splenocytes secreting human IgG-specific antibody of 7 to 10 animals treated for 3 months and sacrificed at 12 months of age. Statistics: one-way ANOVA. 3xTg-AD, triple-transgenic mouse model of Alzheimer’s disease; ANOVA, analysis of variance; ctrl, control (vehicle); ELISA, enzyme-linked immunosorbent assay; IgG, immunoglobulin G; IVIg, human intravenous immunoglobulin; MFI, mean fluorescence index; n.d., not detected; NonTg, non-transgenic.