Fig. 6.

Trem2^R47H induces age/disease-dependent dystrophic neurites and axonal damage. a, b Representative confocal images of subiculum in (a) 4- and (b) 12-month-old wild-type, Trem2^R47H, 5xFAD, and 5xFAD/Trem2^R47H mice stained with Amylo-Glo for dense-core plaques (blue) and immunolabeled for neurofilament light chain (NfL, green) and LAMP1 (red) for dystrophic neurites. c, d Quantification of subiculum LAMP1 volume normalized to Amylo-Glo volume shows increased dystrophic neurites at (c) 4-month but not at (d) 12-month with sex-difference in 5xFAD indicated. e–g Measurement of NfL in (e) plasma, (f) soluble fraction reveals consistent increase in NfL level in 5xFAD/Trem2^R47H compared to 5xFAD at both 4- and 12-months of age, and (g) cortical insoluble fraction. h, k Representative higher magnification images of immunolabeled NfL spheroids (green) colocalized with LAMP1 (red) in the subiculum of (h) 4-month-old and (k) 12-month-old 5xFAD and 5xFAD/Trem2^R47H mice. i, j Reduced density of NfL⁺ spheroids (i) but no change in spheroid volume (j) in subiculum of 5xFAD/Trem2^R47H compared to 5xFAD mice at 4-months of age. l, m No difference in number (l) or volume (m) of NfL⁺ spheroids between 5 and 5xFAD/Trem2^R47H despite a sex-difference in 5xFAD at 12-months of age. n = 10–12. Data are represented as mean ± SEM. Two-way ANOVA followed by Tukey’s post hoc tests to examine biologically relevant interactions. Statistical significance is denoted by *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001