A-beta peptide signatures in brains, CSF and blood plasma from APP23 transgenic mice

APP23 transgenic mice overexpress swedish mutant human Amyloid Precursor Protein under control of the Thy-1 promotor. In an age dependent fashion, the mice develop some of the typical pathological features observed in Alzheimer's disease brains (Sturchler-Pierrat C. et al., Proc Natl Acad Sci USA 1997, 13287–13292). We have analyzed the Aß peptide patterns in EDTA-plasma, CSF, forebrain, brainstem and cerebellum from APP23 mice aged 3, 7, and 15 months. Aß peptides comigrating with synthetic Aß(1–37), (1–38), (1–39), (1–40), (1–42) were detected in all of the samples. In forebrains, but not in brainstem and cerebellum, all five of the different Aß peptides accumulated massively between 7 and 15 months of age. The patterns of Aß peptides extracted from forebrains of APP23 mice were compared with samples from AD patients. In CSF samples from APP23 mice, the total concentration of Aß peptides was approximately 6 times higher than in human CSF. We did not observe age related changes in the relative distribution of the different Aß species in CSF from APP23 mice. The Plasma Aß peptides were detected by immunoprecipitation followed by Urea-SDS-PAGE/western blot analysis. Taken together, our findings indicate that total Aß concentrations in CSF and plasma from APP23 mice were substantially higher than in humans, while the relative distribution of the different Aß species was surprisingly similar.

This study was supported by Novartis Pharma AG