Fig. 6.

LDN/OSU-0215111 reduces pTau and inhibits GSK3β. a, b Effect of compound treatment on phosphorylated tau in total lysates (TCL, open bars) and in the Sarkosyl-insoluble (P3, black bars) fraction (n = 4/group). Dashed line represents the expression in the rTg4510 vehicle group. a Long-term compound treatment slightly, but significantly, increased total tau (Tau5) expression in the forebrain and yet reduced phosphorylated (AT8 and PHF1). There was a very significant reduction of total tau in the P3 fraction and subsequent reductions of phosphorylated tau expression. b Single dosing of compound did not change the total forebrain tau expression (Tau5); however, a significant reduction of phosphorylation in PHF1 and a more robust reduction of AT8 phosphorylation were observed. In the P3 fraction, total tau was reduced and, subsequently, so was all aberrant forms of tau. c Basal inhibitory phosphorylation of GSK3β at Ser9 in rTg4510 vehicle mice was similar to control levels (n = 4/group). Compound treatment significantly increased phosphorylation of GSK3β at Ser9 in rTg4510 mice approximately twofolds within 1 h of treatment, and d this increased GSK3β phosphorylation is maintained up to 24 h after a single dose. *P < 0.05, **P < 0.01, ***P < 0.001