Effect of CHF5074 and DAPT treatments on Aβ-related, cellular and molecular parameters. Representative images of amyloid plaques stained with the 6E10 monoclonal antibody in the cerebral cortex (A, C, E) and in the hippocampus (B, D, F) of untreated (vehicle, A, B) and CHF5074-treated Tg2576 mice (C-F) are shown in the figure. CHF5074 dose and animal code number (#) are indicated in each panel. Quantification of plaque immunostaining in both brain areas of untreated (“vehicle”), CHF5074-treated and DAPT-treated animals (indicated by the different bar colours) is shown in panel G. Plasma Aβ40 and Aβ42 levels in the same groups of untreated, CHF5074- and DAPT-treated animals are reported in panel H. The levels of monomeric Aβ and of different Aβ oligomeric species detected with the 6E10 antibody in low-detergent (0.1% Triton-X100, 0.01% Nonidet-P40) and high-detergent (3% SDS, 0.5% Triton X-100, 1% deoxycholate) brain extracts are shown in panels I and J, respectively. Data refer to the quantification of the indicated Tg2576-specific immunoreactive bands (i.e., polypeptides not present in brain extracts from wild-type littermates) in untreated Tg2576 mice and in Tg2576 mice treated with CHF5074 or DAPT (same number of animals/group as in panel G) by near-infrared fluorescence (NIRF; arbitrary units). Data in panels G-J are expressed as mean ± SEM; **p < 0.01 or *p < 0.05 vs vehicle-treated Tg2576 mice; the number of animals in each group is indicated below the corresponding bar (see Additional file 2: Figure S1 for a representative example of gel fractionation and immunoblot analysis).