Fig. 1

Chronic treatment with FTI LNK-754 reduces amyloid burden and phosphorylated tau in the brains of 5XFAD mice. A Confocal immunofluorescence microscopy showing brain sections from 5-month-old 5XFAD mice treated with vehicle, LNK-754 or lonafarnib immunostained for Aβ42 (red) and NeuN (blue). Scale bar, 1000 μm. Quantification of plaque covered area in the cortex (*p = 0.013) (B) and the hippocampus (**p = 0.0017) (C) in vehicle, LNK-754 or lonafarnib treated 5XFAD mice. Quantification of plaque size in the cortex (D) and the hippocampus (*p = 0.017 between vehicle and LNK-754, **p = 0.0036 between LNK-754 and lonafarnib) (E) in vehicle, LNK-754 or lonafarnib treated 5XFAD mice. PBS (F) and guanidine (*p = 0.028) (G)-soluble Aβ42 from hemi-brain homogenates of 5-month-old 5XFAD mice treated with vehicle, LNK-754 or lonafarnib mice was measured by ELISA and expressed as pg/mg protein. H Immunoblot of brain homogenates from female vehicle, LNK-754 and lonafarnib treated 5XFAD mice probed for phospho-tau (P-tau ser404) and total tau (Tau1). Quantification of P-tau (ser404) normalized to total tau (**p = 0.0027) (I) and total tau normalized to actin (J). Vehicle, n = 11 (5 males, 6 females); LNK-754, n = 10 (4 males, 6 females); lonafarnib n = 10 (4 males, 6 females). Triangles represent males and circles represent females. 1-way ANOVA with Tukey’s post-hoc multiple comparisons test was performed