Fig. 3
Long term HFD increases amyloid plaques deposition and T2D reduces amyloid plaques deposition in APP/PS1 mice. A Long-term HFD administration increased plaque burden (% of cortical volume) while it was significantly reduced in APP/PS1xdb/db mice. No differences were observed at 22 (p = 0.277) and 24 (p = 0.430) weeks of age. However, by 26 weeks of age amyloid plaque burden was significantly increased on animals on HFD and reduced burdens were observed in APP/PS1xdb/db animals [F(3,311) = 13.447, ₸₸p < 0.001 vs. APP/PS1-RD and APP/PS1-HFD, ##p < 0.01 vs. APP/PS1-HFD] and similar profiles were observed afterwards (week 28 [F(3,280) = 6.73, **p < 0.001 vs. rest of the groups], week 30 [F(3,289) = 13.25, **p < 0.001 vs. rest of the groups, ##p < 0.01 vs. APP/PS1-HFD], week 32 [F(3,299) = 17.99, **p < 0.001 vs. rest of the groups, ##p < 0.01 vs. APP/PS1-HFD]. B Illustrative images of cortical regions used to analyze plaque deposition in 32 week-old mice. Blood vessels are labeled in red (Texas Red dextran 70KD) and amyloid in blue (methoxy-XO4). Scale bar = 50 µm. C Amyloid plaques size was smaller in the mixed colony and individual biweekly assessment revealed that plaque size was even further reduced in APP/PS1xdb/db mice when compared with the rest of the groups (week 22 p = 0.561 vs. APP/PS1, week 24 ╫p = 0.021 vs. APP/PS1, week 26 [F(3,1638) = 16.079, **p < 0.001 vs. rest of the groups, ‡‡p < 0.001 vs. APP/PS1-RD and APP/PS1-HFD], week 28 [F(3,1638) = 15.371, **p < 0.001 vs. rest of the groups, ‡‡p < 0.001 vs. APP/PS1-RD and APP/PS1-HFD], week 30 [F(3,1995) = 11.003, **p < 0.001 vs. rest of the groups, ‡‡p < 0.001 vs. APP/PS1-RD and APP/PS1-HFD], week 32 [F(3,2980) = 5.076, ‡‡p < 0.001 vs. APP/PS1-RD and APP/PS1-HFD]). D Biweekly assessment revealed an increase in the number of new amyloid plaques in APP/PS1 animals on HFD when compared with the rest of the groups in the long term (week 22 p = 0.501, week 24 p = 0.976, week 26 [F(3,315) = 2.35, p = 0.079], week 28 [F(3,284) = 4.20, ##p = 0.006 vs. APP/PS1-HFD], week 30 [F(3,302) = 8.76, **p < 0.001 vs. rest of the groups], week 32 [F(3,316) = 27.70, **p < 0.001 vs. rest of the groups]) (APP/PS1-RD n = 4 and 47–65 fields, APP/PS1-HFD n = 4 and 49–79 fields, APP/PS1 n = 7 and 77–112 fields, APP/PS1xdb/db n = 4 and 47–91 fields) (mean ± SEM)