Fig. 3

Linear Aβ deposition and exponential tau accumulation across disease progression in TgF344-AD rats. Aβ and tau pathology were assessed in the hippocampus (HP) and entorhinal cortex (EC) of 9-, 12- and 15-month-old TgF344-AD rats (n = 5–6 rats/age). a Representative HP and EC images of 6F3D staining for Aβ demonstrate extensive plaque coverage at 15 months of age. b PHF1 staining indicates dystrophic neurites [plaque-associated (PA)] and tangle inclusions [non-plaque-associated (NPA); inset] of hyperphosphorylated tau. c Quantification of plaque coverage in HP and EC demonstrates linear accumulation of Aβ across age. NPA (d) and PA (e) tau inclusions also increased with age but in an exponential manner, notably between 12 and 15 months of age, and to a significantly greater degree in EC than HP. f Quantification of PA inclusions per plaque in CA1, DG and EC determined significant effects of age and region on plaque area covered by tau dystrophic neurites (n = 30 plaques/region in each cohort of 5 rats/age). Significantly greater plaque area was covered by tau inclusions in EC compared to DG and CA1 at all ages, and DG compared to CA1 at 9 and 12 months. g Linear relationship between plaque size and number of tau-positive dystrophic neurites, demonstrating significantly more neurites per plaque with age, most prominently at 15 months (9-month: Y = 0.003 X + 4.52; 12-month: Y = 0.004 X + 6.15; 15-month: Y = 0.009 X + 2.57; n = 90 plaques in each cohort of 5 rats/age). Scale bars, 200 μm (a) and 20 μm (b). Data are mean ± SEM (f) or 95% confidence intervals (c–e, g); two-way ANOVA with Holm-Sidak post hoc test (f), linear regression (c, g), non-linear exponential growth regression (d, e); *P < 0.05, **P < 0.01, ***P < 0.001