Distribution of axons containing human tau in middle molecular layer (MML) of dentate gyrus is altered in the presence of amyloid plaques. The MML of the dentate gyrus of (A) rTgTauEC and (B) APP/PS1 × rTgTauEC mice contains human tau-positive axons and terminals, labeled by Tau13 antibody (green), surrounding the densely-packed dentate granule cells (white). Scale bar = 100 μm. C, E. In the absence of amyloid plaques, human tau-positive (Tau13 antibody) axon terminals in the MML appear evenly distributed. D, F. However, in APP/PS1 × rTgTauEC mice, the distribution of tau appears patchy (open arrowheads) in regions positive for plaques. Furthermore, in rTgTauEC mice (C, E), the projection of human-tau positive (Tau13 labeled) neurons is limited to the MML; however, in APP/PS1 × rTgTauEC mice (D, F), tau-positive axons are visible in the OML (solid arrowheads), particularly in the vicinity of amyloid plaques (magenta). Scale bar = 50 μm. IML = inner molecular layer; MML = middle molecular layer; OML = outer molecular layer.