Figure 2
Amyloid pathology in db/AD mice. (a - d) Aβ deposition (4G8 IHC) in mouse neocortex (~8 months old: magnification: 4×). db/AD (a) and AD (c) mice displayed amyloid-containing plaques, while db (b) and WT (d) mice did not. The db genotype significantly upregulated both PS1 expression (p < 0.002 for db overall: e) and tau phosphorylation (p < 0.003 standardized to total tau: f) in the brain (middle-aged: n = 10 F/12 M db wild-type; 13 F/11 M db homozygotes; 22 F/28 M heterozygotes). The results are similar for phosphor-tau when it is not standardized to total tau (not shown) (g) Aβ oligomers were significantly increased in diabetic (db and db/AD) mice (p < 0.001 for db overall, WT, n = 8; db, n = 8; AD, n = 8; db/AD, n = 7) compared to non-diabetic mice. Additionally, oligomers were significantly higher in db/AD compared to AD mice (# = p < 0.0005). (h) Young (3 month old) db/AD mice did not have significantly more Aβ than AD mice (n = 5 F/1 M WT; 5 F/1 M db; 3 F/3 M AD; 3 F/3 M db/AD: p < 0.29). (i) Total Aβ (Ab42.5/4G8), (j) Aβ1–40 (Ab42.5 / 13.1.1), and (k) Aβ1–42 (Ab2.1.3 / 4G8) all increased with age (p ≤ 0.0001); the db genotype had no overall effect, although there was a modest reduction in Aβ1–42 (p ≤ 0.01). * = p ≤ 0.05, relative to db WT. N = 77 [genotype, age (6–7 mo./12 mo.): WT, n = 13/8; db, n = 13/8; AD, n = 9 / 8; db/AD, n = 11/7)].