Multiple-doses subcutaneous administration of C004019 induces tau clearance in 3xTg-AD mice. C004019 (3 mg/kg) or the vehicle was injected subcutaneously into 9.5 m-old 3xTg AD mice (every 6 days for a total of 5 times in one month), and then different types of tau proteins were measured. (A-H) C004019 decreased both soluble and insoluble tau proteins in hippocampal and cortex extracts measured by Western blotting. (I-L) C004019 decreased oligomeric tau in hippocampus and cortex extracts measured measured by Western blotting using antibody T22. (M-N) C004019 decreased p-tau (AT8 and pS404) measured by immunohistochemical (Scale bar: 50 µm). (O-Q) C004019 decreased the aggregated tau levels measured by Thioflavin S staining (Scale bar: 50 µm) with no significant effects on plague. (R-S) C004019 had no significant effects on Aβ plaque measured by Congo red staining (Scale bar: 50 µm). Data were expressed as mean ± SEM, *P < 0.05, **P < 0.01, ***P < 0.001, vs. Vehicle. Data were analyzed by Student's t-test.