Fig. 1. Evolution of senile plaques with age in APPswe/PS1dE9 mice 4, 6, 8, 10 and 12 months old. Data are representative of 3–10 sections (including the areas located under the cranial window) from 3 to 5 animals, and equivalent regions were selected for each animal. One-way ANOVA or Kruskal–Wallis followed by Tamhane or Mann–Whitney U tests with Bonferroni adjustment when necessary. Amyloid beta deposits measured after thioflavin S staining: (A) Plaque number; (B) mean plaque area (F_4,52 = 4.77; *p = 0.002 vs. 4 months old group); (C) plaque burden (F_4,52 = 35.949; *p < 0.001 vs. 4 months old group; †p < 0.001 vs. 6 months old group; ‡p < 0.001 vs. 10 months old group). Amyloid beta deposits measured after 3D6 immunohistochemistry: (D) plaque number (*p < 0.001 vs. 4 old group; †p < 0.001 vs. 6 months old group); (E) mean plaque area (F_4,153 = 10.863; *p < 0.001 vs. 4 months old group); (F) plaque burden (F_4,153 = 27.722; *p < 0.001 vs. 4 months old group; †p < 0.001 vs. 6 months old group).

Fig. 2. Illustrative example of senile plaques evolution with age after thioflavin S staining in coronal hemibrain sections from APPswe/PS1dE9 mice. (A) 4 months; (B) 6 months; (C) 8 months; (D) 10 months; (E) 12 months. Scale bar = 0.75 mm.

Fig. 3. Whole brain amyloid angiopathy progression with age in APPswe/PS1dE9 mice after thioflavin S staining. Increase in senile plaques is also observed with age: (A) 4 months; (B) 6 months; (C) 8 months; (D) 10 months; (E) 12 months. Scale bar = 0.75 mm.

Fig. 4. Illustrative example of amyloid angiopathy evolution, in a representative vessel segment of a APPswe/PS1dE9 mice, in 6 consecutive imaging sessions. Amyloid angiopathy deposits shown in red and angiogram in blue. Weekly intervals from session 1 to 5 and 5 extra weeks in imaging session 6, where CAA progression can still be observed. New senile plaques are also observed in consecutive imaging sessions. Scale bar = 100 μm.

Fig. 5. Progression of CAA in APPswe/PS1dE9 mice. Trajectories of CAA progression obtained from the in vivo imaging sessions for each mouse were drawn as a function of the age in days for the 5 weekly imaging sessions. Only vessels with small diameters (< 44.2 μm) are represented. The straight dotted line drawn through the data depicts the fitted linear regression model with a slope of 0.17%/day.

Soluble and insoluble amyloid beta 1–40 and 1–42 in APPswe/PS1dE9 mice

Levels of both Tris-extracted (soluble) and formic acid-extracted (insoluble) amyloid beta 40 and 42 in APPswe/PS1dE9 mice 4, 6, 8, 10 and 12 months old, expressed as pmol/g of wet tissue. Data are mean ± standard deviation from 3 animals, and differences are detected by Kruskal–Wallis followed by Mann–Whitney test. No differences were detected for soluble Aβ40 (p = 0.092) at any age under study. Significant increases were observed for soluble Aβ42 (p = 0.031), insoluble Aβ40 (p = 0.036) and insoluble Aβ42 (p = `0.025) as animals grew older (* vs. 4 months, † vs. 6 months, ‡ vs. 10 months) (n.d. not detected; n.r. not reported, only one of the mice showed detectable levels of insoluble Aβ40 or 42).