(A, B) Inhibition of Aβ1-42-induced tau phosphorylation by the addition of purified hFcγRIIb-ED protein. Mouse primary cortical neurons were incubated for 24 hr with 1 μM synthetic Aβ1-42 w/wo 50 μg/ml purified hFcγRIIb-ED and cell extracts were subjected to western blotting (A). The levels of phosphorylated tau (PHF1, CP13, and AT180) were normalized by total tau (TG5). Values are means ± s.e.m.; *p<0.05, **p<0.005, ***p<0.0005, one-way ANOVA (n = 3) (B). (C, D) Prevention of Aβ1-42-induced tau phosphorylation by anti-FcγRIIb antibody (2.4G2). Mouse primary cortical neurons were pre-incubated with 2.4G2 antibody for 2 hr and treated w/wo 1 μM Aβ1-42 oligomers for 24 hr. Cell extracts were analyzed with western blotting using indicated antibodies (C). Levels of phosphorylated tau were quantified by densitometric measurement. Values are means ± s.e.m.; *p<0.05, **p<0.005, ***p<0.0005, one-way ANOVA (n = 3) (D). (E–G) Suppression of Aβ1-42-induced cognitive deficits by coinjection of anti-FcγRIIb antibody. WT mice (8 weeks old) were i.c.v.-injected with PBS or Aβ1-42 (410 pmol) together w/wo either 2 μg IgG or 2.4G2 antibody. The mice (n = 10 for each group) were analyzed by Y-maze (E; **p<0.005, ***p<0.0005, unpaired t-test), novel object recognition (F; **p<0.005, one-way ANOVA), and passive avoidance (G; *p<0.02, **p<0.005, unpaired t-test) tests as described in the methods. Bars represent means ± s.e.m. (H) Inhibition of i.c.v. Aβ1-42-induced tau phosphorylation by anti-FcγRIIb antibody. Brain extracts of the Aβ- and/or antibody-injected mice were subjected to western blotting.