Figure 5.

Combination therapy works equally well in aged animals and young adults. a, Experimental design. The tet-off system was used to delay transgenic APP expression until 12 months of age. Animals were then taken off dox to start APP overexpression and the experiment proceeded as in the younger cohort: after 6 months of transgenic APP expression, animals were treated with dox for 2 weeks before starting the first of 12 weekly antibody injections with either nonspecific IgG (n = 7) or anti-Aβ Ab9 (n = 9). Mice remained on dox for 2.5 months after the final injection and were harvested at 24 months of age. b, Campbell–Switzer silver staining reveals significantly less amyloid in mice treated with dox plus Ab9 than in age-matched animals given control IgG (10× hippocampal sections). c, Individual plaques from dox plus Ab9-treated mice appear as “naked cores” missing the halo of diffuse amyloid that surrounds larger plaques in control mice (63×). d, Quantitation of silver-stained sections demonstrates that dox plus Ab9-treated mice have significantly less amyloid than dox plus IgG controls. e–g, ELISA measurement of Aβ levels confirms the histological findings. Significant reductions were found in Aβ42 [sum of SDS plus FA-extracted 42 (e)], SDS-soluble Aβ [sum of SDS-extracted 40 plus 42 (f)], and FA-soluble Aβ [sum of FA-extracted 40 plus 42 (g)].