Tau immunohistochemistry of transgenic tau L66 (a, b, e, f, i) and L1 (c, d, g, h) mice. Tau immunoreactivity with mAb 7/51 is strong in L66 with prominent intracellular staining in the hilus/CA4 sectors of the hippocampus (a) and in other areas (see Fig. 4). In contrast, mAb AT8 immunoreactivity is seen more frequently in elderly mice with staining apparent in long processes of CA1 (d). Neurons in visual cortex (g) are stained differentially with both mAb 7/51 (brown) and AT8 (red). Amorphous intracellular tau immunoreactivity, visualised using mAb 7/51, in the hilus/CA4 of L1 mice (b) is much weaker than for L66, and absent from the corresponding region in WT mice (c). The presence of pS404 phospho-tau immunoreactivity was seen in hippocampus and cortex and was more intense for L1 late in life. At 3 and 9 months old, L1 and WT animals were similar. It was only at 15 months of age that a prominent difference between L1 and wild-type was observed, with CA1 labelling for pS404-Tau greater in L1 (e) than WT (f). The staining of neurons with this mAb indicates that there are granular accumulations of pS404-Tau immunoreactivity in long processes (h, i). Scale bars 50 µm (a, d); 25 µm (e–g); 20 µm (b, c) and 10 µm (h, i)