Amyloid burden and Aβ levels are slightly delayed by adult onset APP overexpression. A, Silver staining shows forebrain amyloid burden after 2, 4, 6, 9 and 12 mo of transgenic APP overexpression following juvenile (top row) or adult onset (bottom row). B, Quantitation of cortical amyloid burden from silver-stained sections demonstrates that delaying APP overexpression slows initiation of the exponential phase of plaque deposition (p < .001), although once underway the rate of amyloid accumulation is similar in both groups. Post hoc comparisons indicate significant differences in amyloid burden at 9 mo (**p < 0.01) and 12 mo (*p < 0.05) of APP overexpression. n = 3-4 per genotype at each time point. C, D Biochemical measures of Aβ concentration parallel histological measures of amyloid load. After equivalent durations of APP overexpression, adult onset is associated with lower levels of both SDS- and FA-soluble Aβ (Aβ 40 plus 42; p < 0.05 (SDS), p < 0.0001 (FA)). Additionally, the rate of change in FA-soluble Aβ is slower following adult onset (p < 0.001). Post hoc comparisons indicate significant differences in FA-soluble Aβ at 9 mo (*p < 0.05) and 12 mo (***p < 0.001) of APP overexpression. Graphs show mean ± SEM. n = 6-8 per genotype at each time point. Open symbols, juvenile onset; closed symbols, adult onset.