Fig. 4

Acute FTI treatment reduces LysoTracker-Green accumulation in dystrophic neurites surrounding plaques in 5XFAD mice. A Confocal immunofluorescence microscopy showing plaques in cortical brain regions from 5-month-old 5XFAD mice treated for 3 weeks with vehicle, LNK-754, or lonafarnib labeled with thiazine red (red) and LysoTracker-green (green). Scale bar, 25 μm; high magnification images, 10 μm. Maximum intensity projections of 30 μm Z-stack images are shown. B Quantification of thiazine red covered area for individual plaques in vehicle, LNK-754 or lonafarnib treated 5XFAD mice. C Quantification of LysoTracker-green covered area in dystrophic neurites normalized to thiazine red area per plaque in vehicle, LNK-754 and lonafarnib treated 5XFAD mice (***p = 0.0007 between vehicle and LNK-754, *p = 0.017 between vehicle and lonafarnib). D Quantification of the average size of dystrophic neurites, measured by quantifying average object area of LysoTracker-Green in dystrophic neurites per plaque (*p = 0.026 between vehicle and LNK-754, *p = 0.035 between vehicle and lonafarnib). Correlations of plaque area plotted against LysoTracker-Green object area in vehicle (E) LNK-754 (F) and lonafarnib (G) mice. Vehicle, Rsq = 0.0062, p = 0.3482; LNK-754, Rsq = 0.2664, p < 0.0001; Lonafarnib, Rsq = 0.1322, p = 0.0002. Vehicle, n = 5 (2 males, 3 females); LNK-754, n = 5 (2 males, 3 females); lonafarnib n = 5 (2 males, 3 females). Triangles represent males and circles represent females. 1-way ANOVA with Tukey’s post-hoc multiple comparisons test was performed in B-D and linear regression was performed in E-G