Propagation of tauopathy along neural circuits is exacerbated by amyloid pathology. Low magnification view of horizontal sections of 16 month old brains from (a) rTgTauEC and (i) rTgTauEC x APP/PS1 mice, labeled with a human-specific tau antibody Tau13 (green) and cell bodies stained with DAPI (blue; scale bar = 1 mm), reveal increased propagation of tauopathy in rTgTauEC x APP/PS1 mice compared with rTgTauEC mice. (b,
j) Higher magnification of layers of the DG showing the middle molecular layer (MML) and granule cell layer (GC; scale bar = 50 μm); and (c,
k) CA1 fields of the hippocampus (scale bar = 50 μm) show human-tau positive cells in brain regions synaptically connected to the EC. Note apparent degeneration of the MML of the DG in rTgTauEC x APP/PS1 mice. In rTgTauEC x APP/PS1 mice, but not rTgTauEC mice, human tau is observed in brain regions distal to the EC such as somatosensory cortex (e,
m) and accessory olfactory areas (f
n; scale bars 100 μm). (d,
l) Immunolabeling for Alz50 (red; scale bar 50 μm), a marker of abnormally folded tau, was evident in neurons in the GC layer of the DG and increased in rTgTauEC x APP/PS1 mice compared with rTgTauEC mice. Again, loss of Alz50-positive terminals in the MML was observed. (g,
h) Quantification of human tau-positive neurons in the DG granule cells immunolabeled with Tau13 (rTgTauEC, N = 7; rTgTauEC x APP/PS1, N = 10) or Alz50 (rTgTauEC, N = 7; rTgTauEC x APP/PS1, N = 7) in 16-month-old animals. Significantly more neurons containing human tau were observed in rTgTauEC x APP/PS1 mice compared with rTgTauEC mice, indicating increased propagation in this group. (o,
p) In 10-month-old mice, human tau propagation (Tau13) from the EC to the DG was observed only in rTgTauEC x APP/PS1 mice (rTgTauEC, N = 7; rTgTauEC x APP/PS1, N = 7). Values represent mean ± s.e.m; *P < 0.05.