Tau multimers in rTg4510 mice. A, Western blot of total extracts from 3.5-month-old rTg4510 and age-matched tTa animals (without mutant P301L tau transgene). Tau migrating at ∼55 kDa can be detected with the human-specific E1 antibody in rTg4510 but not in tTa animals. Tau multimers migrating at ∼170 (called tau170) and ∼140 kDa (called tau140) can be seen in rTg4510 but not in age-matched tTa animals, when film is exposed for a longer time. B, Schematic location of epitopes on tau that are recognized by phosphorylation-independent antibodies tau12, E1, TauC3, and tau46. Tau12 and E1 are N-terminal, whereas tau46 is C-terminal. TauC3 (which does not detect tau multimers) is selective for tau cleaved at Asp421. C, Tau multimers are detected in total brain extracts from 3.5-month-old rTg4510 with a variety of tau antibodies (E1, CP13, PHF1, PS422, AT8, and T46). Age-matched tTa animals (without mutant P301L tau transgene) were used as a control. Tau170 and tau140 are seen by E1, CP13, PHF1, and T46, whereas PS422 and AT8 selectively detects tau170. D, Dephosphorylation leads to disappearance of tau170, although tau140 is still present.