Figure 1
(a) Chemical structure of RO5506284 ([8-(4-Fluoro-phenyl)-[1,2,4]triazolo[1,5–a]pyridin-2-yl]-[1-(3-methyl-[1,2,4]thiadiazol-5-yl)-piperidin-4-yl]-amine). (b) In vitro potency of RO5506284 in human H4 and mouse N2A cells overexpressing Swedish mutant APP on Aβ42 secretion; and effect on Notch processing in the HEK293 cell reporter assay. (c) Reduction of brain Aβ42 was determined in an acute study where the animals were killed 4 h post-treatment. Each bar represents the mean of n=5 (n=4 at 100 mg kg−1) animals. Young 3-month old, pre-amyloid Tg mice were used for this study to determine the changes of soluble brain Aβ following acute γ-secretase modulation with RO5506284. A dose-dependent decrease of brain Aβ42 (upper panel) and a corresponding increase of Aβ38 (mid panel) can be observed, without major effect in total Aβ levels (lower panel). *indicates statistically significant at P<0.05; ***indicates statistically significant at P<0.001.
