Fig. 2
Prediabetes and T2D accelerate CAA progression rates in APP/PS1 mice in vivo and in real time. A Assessment of CAA deposition revealed that HFD-induced prediabetes as well as T2D significantly increased CAA deposition as disease progressed. When individual imaging sessions were compared no differences were detected between APP/PS1 and APP/PS1xdb/db mice at 22 weeks of age (p = 0.099), however significant differences were observed at 24 weeks of age when APP/PS1 and APP/PS1xdb/db mice were compared (**p < 0.01 vs. APP/PS1). By 26 weeks of age CAA burden was higher in APP/PS1-HFD animals and even higher burdens were observed in APP/PS1xdb/db mice [F(3,690) = 15.056, **p < 0.001 vs. rest of the groups; ††p < 0.01 vs. APP/PS-RD]. From 28 weeks of age on, both HFD-induced prediabetes and T2D significantly increased CAA deposition in APP/PS1 animals (week 28 [F(3,617) = 18.42, ‡‡p < 0.0.1 vs. APP/PS1-RD and APP/PS1]; week 30 [F(3,589) = 25.98, ‡‡p < 0.0.1 vs. APP/PS1-RD and APP/PS1]; week 32 [F(3,503) = 26.16, ‡‡p < 0.0.1 vs. APP/PS1-RD and APP/PS1]) (APP/PS1-RD n = 4 and 42–81 vessel segments, APP/PS1-HFD n = 4 and 86–118 vessels segments, APP/PS1-RD n = 7 and 160–262 vessel segments, APP/PS1xdb/db and 233vessel segments) (mean ± SEM). B Illustrative example of individual vessels labeled with methoxy-XO4 to quantify CAA deposition along imaging sessions. CAA is isolated from the background and set white in binary images. Scale bar = 100 µm. Illustrative pseudocolor images of cortical regions (upper panel) were used to analyze CAA deposition along the biweekly imaging sessions in all groups under study (bottom panel). Blood vessels are labeled in red (Texas Red dextran 70KD) and amyloid in blue (methoxy-XO4). Scale bar = 100 µm. C) CAA deposition was increased in smaller vessels from APP/PS1-HFD mice whereas larger vessels from AD-T2D mice were more severely affected (diameter ≤ 25 µm: 26 weeks of age [F(3,256) = 2.49, p = 0.061], 28 weeks [F(3,224) = 3.89, ‡p = 0.010 vs. APP/PS1-RD and APP/PS1], 30 weeks [F(3,256) = 9.67, ‡‡p < 0.01 vs. APP/PS1-RD and APP/PS1], 32 weeks [F(3,250) = 10.71, **p < 0.01 vs. rest of the groups]; diameter > 25 ≤ 50 µm: 26 weeks of age [F(3,267) = 7.86, **p < 0.01 vs. rest of the groups], 28 weeks [F(3,236) = 8.13, ‡‡p < 0.01 APP/PS1-RD and APP/PS1, ††p < 0.01 vs. APP/PS1-RD], 30 weeks [F(3,223) = 13.94, ‡‡p < 0.01 APP/PS1-RD and APP/PS1], 32 weeks [F(3,174) = 18.44, ‡‡p < 0.01 APP/PS1-RD and APP/PS1]; diameter > 50 µm: 26 weeks of age [F(3,159) = 14.39, **p < 0.01 vs. rest of the groups], 28 weeks [F(3,149) = 14.82, ‡‡p < 0.01 vs. APP/PS1-RD and APP/PS1], 30 weeks [F(3,102) = 8.78, **p < 0.01 vs. rest of the groups], 32 weeks [F(3,71) = 12.79, **p < 0.01 vs. rest of the groups]) (mean ± SEM)