Fig. 1

Tau4RTg2652 animals accumulate conformationally altered abnormally phosphorylated pathological tau. Age matched non-Tg mice exhibit no detectable phosphorylated tau by AT8 immunohistochemistry (a) as compared to TauTg2652 mice (b) which are immunoreactive as early as 3 months of age. Likewise, non-Tg mice exhibit no detectable pre tangle conformations of tau by MC1 immunohistochemistry (c) as compared to TauTg2652 mice (d) where pre-tangles are evident as early as 3 months of age. Scale bars = 500 μm. (e) Immunoblot analysis of sequential extraction of detergent insoluble tau protein was detected with pan-tau antibody 17-25 [14]. Brain hemispheres were homogenized and lysates compared from 3 mice per group (3 month old, 6 month old, 20 month old tau Tg compared with Non-Tg mice). Total extracts were first probed for tau and actin to determine total tau levels relative to loading control. To measure detergent insoluble tau species, mouse brains were subjected to a sequential extraction using buffers of increasing solubilizing strength. Note the FA fraction represents detergent insoluble tau. Results are shown for 3 different nTg mice, and for 3 different Tau4RTg2652 mice for each age group