Vaccination with 3A oligomer improves spatial cognitive deficits in Tg2576 mice. A. 3A peptide-vaccinated and other vaccination groups of Tg2576 mice were evaluated using a spatial reference paradigm and compared with control treated mice vaccinated with colloidal gold and adjuvant. Mice were trained on the spatial reference version of the Morris water maze task after treatment. Besides 3A oligomer- also Aβ oligomer-, IAPP oligomer- and Aβ fibril-vaccinated mice also showed significant improvement (***p < 0.001) as compared to control vaccinated mice (Figure 1A). B. In probe trial during 1.5 hr and 24 hr testing, all vaccinated Tg2576 mice also display significantly shorter latencies than control vaccinated Tg2576 mice (ANOVA, ***p < 0.001, **p < 0.01 and *p < 0.05). C. Vaccination prevents contextual fear memory deficits in a mainly amygdala-dependent task. Mice were tested for retention of memory for fear-associated environments 24 hrs after training. Mice were taken out after 180 s if they did not cross over. At 24 hrs all the vaccinated mice showed significant improvement (***p < 0.001 for 3A vaccinated, **p < 0.01 for Aβ fibril, Aβ oligomer and IAPP oligomer vaccinated mice). D. Context dependent object recognition testing reveals that control vaccinated Tg2576 mice are impaired, spending an equivalent amount of time exploring both objects. At 14 months all the vaccinated mice showed improvement as compared to control vaccinated (*p < 0.05).