Figure 1.

Pathology in aging htau mice was characterized by cell-body accumulation of phosphorylated and conformationally altered tau that aggregated into classic paired helical filaments and neurofibrillary tangles. An antibody to tau phosphorylated at serine 202 (CP13) labeled neurons in 16-month-old htau mouse piriform cortex (A) and hippocampus (B) in a manner that resembled that in neurofibrillary tangles of human brain (C). Neurons were also positive for MC1 (an AD conformation-specific antibody) in the piriform cortex (D) and hippocampus (E) of 16-month-old htau mice. PHF1 (Ps396/404) antibodies labeled distorted cortical neurons in the neocortex (F) and hippocampus (G) of 16-month-old htau mice. Thioflavine-S, a fluorescent histochemical stain commonly used to detect neurofibrillary tangles, did not detect any in control mice (H) but did reveal intensely labeled neurons in htau mice shown here in the piriform cortex (I) and hippocampus (J) of 15-month-old htau mice. Scale bars, 10 μm. Electron microscopy of Sarkosyl-insoluble material isolated from 16-month-old htau mice that were immunogold labeled with antibodies specific for phosphorylations on tau at serine 202 (CP13; K) and serines 396/404 (PHF1; L) confirmed the presence of paired helical filaments. Very similar results are found in mice aged 16-22 months, and representative data are shown.