Biochemical detection of aggregated P301S tau indicates that fibrillar tau may accumulate over time in these animals. Therefore, we performed additional histological analyses using markers for more advanced tau pathology. The AT100 antibody was used to detect abnormal tau phosphorylation on residues Thr 212/Ser 214, also present on PHF (Fig. 4f)28. To further substantiate the presence of tau deposition, we used the thioflavine-S and Gallyas silver stainings, which reveal neurofibrillary deposits of PHF. We observed the presence of AT100-positive neuronal cell bodies and processes only in the group of mice injected with the AAV-P301S vector (Fig. 4f). These neurons were mainly distributed in the cortex and hippocampus 7 months after vector injection. In the same samples, we also observed the presence of neurons positive for thioflavine-S in the cortex (Fig. 4g), as well as the deposition of argyrophilic filamentous inclusions stained with Gallyas (Fig. 4h). The filamentous inclusions were found in the neuronal soma or appeared as structures resembling neuropil threads (Fig. 4h). Of note, we did not detect any sign of advanced tau pathology in any of the mice injected with AAV-WT. Altogether, these data confirmed the progressive modification of tau leading to misfolding and aggregation, which was most evident for the P301S pathogenic mutation of tau.