Figure 5.

hTau transgenic mice unilaterally inoculated in the hippocampus with sarkosyl-insoluble fractions from AD homogenates at the age of six months and killed at the age of nine months show abundant abnormal deposits in the CA1 region of the hippocampus (CA1) and dentate gyrus (DG). AT8-immunoreactive deposits are seen in CA1 region (A), and dentate gyrus and hilus (D). Tau deposits are stained with anti-4Rtau antibodies (B,E), and more strongly with anti-3Rtau antibodies (C,F). Phospho-tau deposits in hTau transgenic mice are dense and flame-shaped, reminiscent of neurofibrillary tangles. Immunoreactivity to tau-P Ser422, PHF1, MAP2-P, and tau-N Tyr29 is strongly positive (G, H, K and J, respectively). MC1 immunoreactivity is restricted to a few neurons (I); in this field, one neuron has small granular deposits (right arrow) and the other a dense round inclusion (left arrow). CK1-δ (L), GSK-3β-P Ser9 (M), AKT-P Ser473 (N), and PKAα/β-P Tyr197 (O) granular immunoreactivity (arrows) appears in affected neurons in inoculated hTau mice. Sections are consecutive and obtained from the same inoculated hTau mouse. Paraffin sections slightly counterstained with haematoxylin, bar = 50 µm. The graph shows quantitative densitometry for anti-3Rtau and anti-4Rtau staining expressed as a percentage of arbitrary units per area in CA1 and dentate gyrus (DG) regions in inoculated hTau mice surviving six months after injection. Results were analyzed with Student’s t-test. Differences between anti-3Rtau and anti-4Rtau staining within the same region in consecutive slices were considered statistically significant at * p < 0.05.