Fig. 2

Decreased levels of LAMP1 in dystrophic neurites is associated with reduced plaque burden in LNK-754-chronically treated 5XFAD mice. Confocal immunofluorescence microscopy showing cortical (A) and hippocampal regions (B) from 5-month-old 5XFAD mice treated with vehicle, LNK-754, and lonafarnib immunostained for Aβ42 (red) and LAMP1 (green). Scale bar, 100 μm. Quantification of LAMP1 covered area in dystrophic neurites the cortex (*p = 0.037) (C) and hippocampus (**p = 0.0012) (D) in vehicle, LNK-754 and lonafarnib treated 5XFAD mice. Quantification of the ratio of dystrophic neurite LAMP1 covered area normalized to plaque area in cortical (*p = 0.030) (E) and hippocampal (*p = 0.011) (F) brain areas. Correlations of plaque area (Fig. 1) in the cortex (G) and hippocampus (H) plotted against LAMP1 fluorescence intensity in dystrophic neurites (Fig. S5E, F). 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 in C-F and linear regression was performed in G and H. Vehicle; Rsq = 0.0170, p = 0.719, LNK-754; Rsq = 0.699, p = 0.0097, Lonafarnib; Rsq = 0.0521, p = 0.526 in (G). Vehicle; Rsq = 0.0527, p = 0.524, LNK-754; Rsq = 0.289, p = 0.141, Lonafarnib; Rsq = 0.0006, p = 0.9495 in (H)