Figure 4.

Active and passive Aβ immunizations prevented SYN loss in the frontal neocortex and hippocampal OML (Hippoc. Molec. Layer) of PDAPP mice. For active immunization, 12-month-old PDAPP mice were treated with full-length Aβ [Aβ(1-42)] or with different Aβ fragments conjugates [Aβ(1-5),Aβ(3-9),Aβ(15-24)] for 6 months, as described in Materials and Methods. Control PDAPP mice received either vehicle only or a reverse peptide, Aβ(5-1). For passive immunization, 12-month-old PDAPP mice were treated for 6 months with either 3D6 [directed against Aβ(1-5)] or 12B4 [directed against Aβ(3-7)], dosed at 10 mg/kg for each weekly injection as described in Materials and Methods. Control PDAPP mice received injections of an irrelevant antibody or vehicle only. All antibodies were of the IgG2a isotype. SYN levels were analyzed in the frontal neocortex and hippocampal OML of 18-month-old PDAPP mice after completion of immunization. Significant improvements of SYN levels over controls were found after active immunization with Aβ(1-42), Aβ(1-5), and Aβ(3-9), but not Aβ(15-24) (a1, b1), and after passive immunization with either of two N-terminal Aβ antibodies (b1, b2). In these groups, SYN levels were not significantly different from that of nontransgenic mice or 12-month-old untreated PDAPP mice (see Figs. 2, 3). The results shown are means ± SEM. ^**p < 0.01, ^***p < 0.001, by Dunnett's post hoc test (n = 16-25 mice per group).