A comparison of conventional versus push-pull microdialysis for the detection of amyloid β in the mouse brain

using a sensitive plate based ELISA system (MSD). Results: Unlike gamma secretase inhibitors, which demonstrate a “potency shift" when the concentration of substrate is very high as in systems overexpressing APP (Burton et al 2008), the potency of GSMs does not demonstrate a systematic shift in overexpressing systems. The pattern of modulation of As peptides was consistent across model systems and specific to each structurally distinct GSM, with some demonstrating a decrease in As42 and an increase in As38 and others demonstrating a decrease in both As42 and 38. Conclusions: The physiological significance of these alterations in cleavage site is not well understood, but appears to be driven by unique interactions of GSMs with gamma secretase.