Tau pathological hallmarks do not arise in the entorhinal cortex until 26 months of age. Coronal mouse brain sections (30 μm) were prepared from 3xTg-AD mice sacrificed at 2 (A, I, Q), 3 (B, J, R), 6 (C, K, S), 9 (D, L, T), 12 (E, M, U), 15 (F, N, V), 18 (G, O, W), and 26 months of age (H, P, X) and were processed for immunohistochemistry to detect the human tau P301L mutant transgene product using the HT7 monoclonal antibody (A–H), human phospho-tau (Thr231) using the AT180 monoclonal antibody (I–P), and paired helical filament pathology using the PHF-1 monoclonal antibody (Q–X). Entorhinal cortex was examined for patterns of immunopositivity and photomicrographs were obtained at 10×. The insets in panels H, P, and X represent a 40× digitally magnified images of designated photomicrographs for better visualization of immunopositive cell/pathology. Scale bar in D represents 200 μm.