Fig. 1.
Pharmacological inhibition of BACE1 reduces soluble Aβ levels. a Six-week-old mice were treated for 14 days with vehicle or NB-360 and were sacrificed thereafter to determine Aβ levels. BACE1 inhibitor treatment significantly reduced the levels of Aβ40 and Aβ42 in forebrain and plasma. Data presented as mean ± SEM with **p < 0.01; ***p < 0.001; n = 6 mice per group; t-test. b In vivo two-photon imaging was performed weekly in the somatosensory cortex of APPPS1xVGLUT1Venus mice. c Mice were reimaged repetitively from 3 to 7 months of age. After four timepoints of baseline imaging (at an age of 4 months), mice were administered vehicle or NB-360 in food pellet until 7 months of age. d In the same region of interest, Methoxy-X04 stained β-amyloid plaques (cyan) and VGLUT1Venus positive glutamatergic boutons (green) were repetitively imaged. The image series shows a plaque from a vehicle-treated mouse. Scale bar represents 40 μm. e Time series of representative 3D rendered plaques of the vehicle (light gray) and NB-360 (dark gray) treated cohorts. Scale bar represents 60 μm. f, g For the same plaques as in e the radii at consecutive timepoints were calculated, fitted with monophasic association functions, and h growth rates at each timepoint were derived