Figure 5

Kinetics of homozygous E8 mice. Immunohistochemical analysis of hom E8 animals from the age of 1–12 months compared to wt animals (A-F). Staining with 6E10 revealed progressive increase of total Aβ immunoreactivity from the age of 1–9 months with a decline at 12 months (A). Increase of pE3-Aβ reactivity from 3–9 months and decline at 12 months (B) is accompanied by GFAP reactivity (C). Apoptotic processes are indicated provided by progressive caspase 3 activity beginning at the age of 3 months (D). The lateral striatum shows a progressive decrease of DARPP-32 reactivity of neuropil from the age of 6 months (E). The different processes result in decreased NeuN positive cells of E8 animals indicating cell loss beginning in at the age of 6 months (F). Quantification of pE3-Aβ positive cells in the striatum of hom E8 animals revealed exponential increase from 3–9 months and declining numbers at the age of 12 months to the level of 6 months (G); data were analyzed by one-way ANOVA followed by Newman-Keuls post-hoc test and represent means ± SEM; ** p < 0.01; *** p < 0.001; n = 4–8 animals per group. Quantification of protein levels by ELISA of hom E8 brains revealed an progressing increase of total Aβ until the age of 6 months; pE3-Aβ protein levels are detectable from the age of 6, reaching its maximum at the age of 9 and declining at 12 months (H); protein values are expressed as percentage of hom E8 brains at the age of 6 months; data were analyzed by one-way ANOVA followed by Newman-Keuls post-hoc test and represent means ± SEM; ** p < 0.01; *** p < 0.001; n = 3–9 animals per group;<LOQ (below level of quantification).