Figure 1

Experiment timeline and anti-human IgG tires. (A) Four-month-old APdE9 transgenic mice and their wild-type littermates received once weekly intraperitoneal injection of either hIVIG (1 g/kg) or saline for 3 months (Experiment 1) or for 8 months (Experiment 2). Mice were sacrificed one week after the last injection and brain samples were collected. In Experiment 2, blood samples were also collected at 7.5 months (upward arrows). (B) Anti-human IgG titers developed by APdE9 mice treated for 3 months with hIVIG (n = 17) compared to saline (n = 2). Sera were collected at the end of treatment period and anti-human IgG titers were estimated by ELISA. Titers are expressed in log10 scale and titers only > 200 were considered significant. (C) Anti-human IgG titers developed at 6 and 12 month’s time point by 4-month-old female APdE9 (n = 16) and wild-type (n = 16) mice, treated for 8 months with hIVIG compared to saline (n = 4; one for each genotype at 6 and 12 months of age). Titers > 200 were considered significant. Circles and triangles represent wild and APdE9 mice, respectively. It is evident from (B) and (C) that not all mice developed significant anti-human IgG titers. Moreover, at terminal sampling point anti-human IgG titers were highly variable irrespective of genotype or treatment duration. (D) Brain sections stained with anti-human IgG antibody and the corresponding anti-human IgG titres in sera as measured by ELISA are shown here. Notice similar patterns of human IgG immunopositivity in hippocampus as we proceed from titres of 50 to as high as 51,200. Scale bar denotes 100 μm. (E) Coronal brain section immunostained with anti-human IgG antibody. The full extent of human IgG penetration in this mouse 389 with highest anti-human IgG titres is displayed. Scale bar denotes 500 μm. Black and red arrows highlight hippocampal and cortical human IgG immunopositivity, respectively. (F) One of the sections from a pair of serial sections is stained with anti-human IgG antibody and the other with double stain for anti-human IgG/congo red. Brain penetration of hIVIG is clearly evident from the presence of numerous hIgG deposits in the hippocampus (red arrows). These hIgG deposits are seen decorating congo red positive amyloid deposits (black arrows). Scale bar denotes 50 μm.