Figure 2From: Amyloid accelerates tau propagation and toxicity in a model of early Alzheimer’s disease 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.Back to article page