immunoconjugate induces potent levels of anti-Aβ and low levels of anti-mannan antibodies in Tg2576 mice. A. Vaccinated mice 7–7.5 months of age produced on average 10.4 μg/ml of anti-Aβ antibodies (approximate titers ≥ 1:10,000) after 6 immunizations. At termination, when mice reached 18–18.5 months of age they still produced low levels of anti-Aβ antibodies (0.8 μg/ml or approximate titers ≥ 1:800). Noteworthy, mice immunized with mannan-BSA did not produce detectable levels of anti-Aβ antibodies (data not shown). B. Mannan-Aβ28 induced primarily IgG1 isotype antibodies, indicative of a Th2 type humoral immune response before resting period (sera were collected on 9th day after the last boost) and after resting period (sera were collected after 11 months). One vaccinated mouse also induced high level of IgM anti-Aβ antibodies. C. After 6 injections vaccinated mice produced low titers of anti-mannan antibodies. Of note, the titers of anti-mannan antibodies dropped dramatically during the intervening 11 months following the final injection (data not shown). (D). Mannan-Aβ28 as well as mannan-BSA induced only low levels of anti-mannan antibodies predominantly of IgG and IgM isotypes in mice immunized with mannan-Aβ28, and IgG isotypes for mice immunized with mannan-BSA. E. Anti-Aβ28 antibodies bind to all species of Aβ42 peptide. One μl of Aβ42 fibrils, oligomers and monomers (45 μM each) were applied in duplicate to a nitrocellulose membrane and probed with sera from mannan-BSA immunized mice (control), sera from mice immunized with mannan-Aβ28, anti-Aβ 20.1 monoclonal antibody and rabbit A11 antibody shown to bind oligomeric forms of Aβ42. (F). Binding of immune mannan-Aβ28 sera to the AD brain section. Binding of antisera was blocked by Aβ1–15 peptide. Original magnification, 20×, scale bar = 100 μm.