Article Figures & Data
Figures
- Figure 1.
Serial spatial learning task. The main task is training on a series of five separate spatial locations (shown), followed by additional training for a total of 10 d (data not shown). For each problem, the hidden platform is in a different location of the pool. The trials-to-criterion data are based on this set of five problems. Swim paths are shown for the first trial of training and for the three criterion trials of each problem only.
- Figure 2.
Visible platform learning. A, There was no difference in escape latency between the PDAPP and non-Tg groups in the prevention study. B, There was a deficit in escape latency in the PDAPP groups on day 1 but not thereafter in the reversal study.
- Figure 3.
Serial spatial learning: trials to criterion measure. Unlike conventional measures of water-maze spatial learning (which use escape latency), the measure of performance is the number of trials taken to learn each spatial problem across five successive spatial problems. A, B, Trials to criterion for the prevention study (experiment 1). Plot of performance for each individual platform (A) and of mean performance across the five locations (B). Overall, the PDAPP groups were impaired, and there was apparently no effect of immunization. C, D, Trials to criterion for the reversal study. Plot shows performance for each individual platform and of mean performance across the five locations. Again, the PDAPP groups were impaired, and there was no effect of immunization.
- Figure 4.
Serial spatial reversal learning: learning capacity measure. Additional training continues for a full 10 d. The learning capacity measure is the total number of spatial locations (problems) learned by each animal over this time. A, Prevention study. B, Reversal study. The PDAPP mice were impaired, and there was no apparent impact of immunization.
- Figure 5.
Correlation between Aβ levels and learning capacity. A, B, Prevention study. Analysis of the relationship between cortical (A) and hippocampal (B) total Aβ levels and learning capacity (LC) revealed a significant negative correlation. That is, animals with very low Aβ levels learned a higher number of platform locations in 10 d. C, D, Reversal study. A similar analysis revealed a trend toward negative correlations between cortical and hippocampal Aβ levels and learning capacity, but these were not significant. E, F, Combined MPL-AF-treated PDAPP animals. No relationships were observed between Aβ levels and performance in adjuvant-treated animals.
- Figure 6.
Learning capacity as a function of Aβ levels and Aβ titers. A, The PDAPP mice (immunized and untreated) were subdivided with respect to cortical Aβ levels. These data reveal that the subgroup with the very lowest Aβ levels were indistinguishable from non-Tg controls and better than PDAPP mice with higher Aβ levels. B, The PDAPP mice (immunized and untreated) were subdivided with respect to hippocampal Aβ levels. The subgroup with the very lowest Aβ levels was indistinguishable from non-Tg controls. C, The PDAPP mice (immunized) were subdivided with respect to Aβ titers. A relationship between antibody titer and performance was observed, but the subgroup with the highest antibody response was still impaired relative to non-Tg controls. Note an apparently exacerbated impairment in immunized mice with a low antibody titer.
Tables
- Table 1.
Total Aβ and Aβ42 levels in the cortex and hippocampus of PDAPP mice and amyloid titer response
Aβ-immunized PDAPP MPL-AF-treated PDAPP % of decrease Prevention Reversal Prevention Reversal Prevention Reversal Cortex Total Aβ n 17 24 17 18 Mean (ng/g) 2109 5188 6068 8342 65.2 37.8 SEM 464 876 1036 749 Aβ42 n 17 24 17 18 Mean (ng/g) 2296 3779 5058 6902 54.6 45.3 SEM 506 631 799 562 Hippocampus Total Aβ n 17 24 17 18 Mean (ng/g) 10379 18394 19199 22849 45.9 19.5 SEM 1904 2164 2562 1868 Aβ42 n 17 24 17 18 Mean (ng/g) 10106 17744 19068 23026 47.0 22.9 SEM 1775 2034 2725 1983 Aβ-immunized PDAPP Aβ-immunized non-Tg Prevention Reversal Prevention Reversal Amyloid titer response n 17 24 17 22 Mean 9662 2644 6769 1809 SEM 2365 214 860 196 - Table 2.
Correlation coefficients between Aβ and antibody titer levels and serial spatial learning performance
Trials to criterion Learning capacity Hippocampus Total Aβ Prevention (n = 17) 0.582* −0.624** Reversal (n = 24) 0.323 −0.238 MPL-AF treated (n = 35) 0.071 −0.06 Aβ42 Prevention 0.447 −0.537 Reversal 0.367 −0.284 MPL-AF treated 0.024 −0.046 Cortex Total Aβ Prevention 0.554* −0.573* Reversal 0.281 −0.334 MPL-AF treated 0.144 −0.013 Aβ42 Prevention 0.317 −0.352 Reversal 0.375 −0.421* MPL-AF treated 0.145 −0.028 Antibody titer Prevention −0.231 0.317 Reversal −0.108 0.072 - Table 3.
Distribution of numbers of PDAPP mice into categories as a function of total Aβ levels
Cortex Total Aβ (ng/g) <1000 <2500 <5000 >5000 Total Aβ-immunized PDAPP 9* 9 12 11 41 MPL-AF-treated PDAPP 2 4 7 22 35 Hippocampus Total Aβ (ng/g) <6000 <13000 <20000 >20000 Total Aβ-immunized PDAPP 13* 7 8 13 41 MPL-AF-treated PDAPP 2 4 10 19 35 -
↵*p < 0.05.
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