Fig. 3

Trem2 H157Y reduces amyloid burden and dystrophic neurites in 5xFAD mice at 8.5 months of age. A-B. Aβ40 (A) and Aβ42 (B) were quantified by ELISA and normalized to WT in cortical guanidine lysates (GND) for each genotype. C-D. Aβ42 oligomer were quantified by ELISA and normalized to WT in cortical TBS (C) and TBSX (D) lysates for each genotype. E. Representative images of amyloid (MOAB2) staining are shown for each genotype. Scale, 400 µm. F-K. Cortical (F–H) and hippocampal (I-K) amyloid plaque area coverages (F, I), densities (G, J) and sizes (H, K) were quantified and normalized to WT mice. L. Representative images of LAMP1 staining for dystrophic neurites are shown. Scale, 400 µm. M–N. Cortical (M) and hippocampal (N) LAMP1⁺ area coverages were quantified and normalized to WT mice for each genotype. A-N. N = 19–24 mice per genotype at 8.5 months of age, mixed sex. Data are presented as Mean ± SEM. Kruskal–Wallis tests with uncorrected Dun’s multiple comparisons were used. O. Aβ42 was quantified by ELISA in the interstitial fluid (ISF) obtained in microdialysis experiments with WT and Hom mice at 3 months of age. At time 0, γ-secretase inhibitor LY411575 was administrated to stop the Aβ production. P. Semilog plot was performed from time 0 to analyze the half-life of Aβ42 clearance. Q. Half-life was calculated and plotted in WT and Hom mice with a normalization to WT mice. O-Q. N = 6–7 mice per genotype at 3 months of age, mixed sex. Data are presented as Mean ± SEM. Unpaired t tests were used in P. Welch’s t test was used in Q. N.S., not significant. * p < 0.05. **p < 0.01