FIGURE 9.

Comparison of fibrillar amyloid plaque accumulation in 3xTg-AD and 5xFAD mice. (A) Representative images of brain hemispheres of WT(B6;129) at 4- and 18-month and 3xTg-AD mice at 4-, 12-, 18-month stained with Thio-S/IBA1. (B) Representative stitched brain hemispheres of WT(B6J) at 4- and 18-month and hemizygous 5xFAD mice at 4-, 12-, 18-month stained with Thio-S/IBA1. (C,D) Quantification for density of Thio-S⁺ plaques in subiculum hippocampal regions in 3xTg-AD and 5xFAD mice showed differences in plaque burden between mouse models and sexes. (E) Quantification for IBA1 immunostaining for microglia in subiculum hippocampal regions reveals age-related differences between mouse models. (F,G) TPM values for Thy1 expression in micro-dissected cortical lysates revealed an age-associated increase in 3xTg-AD, as well as sex-differences driven by female mice. (H,I) TPM values for Thy1 expression in micro-dissected cortical lysates in 5xFAD mice displays a significant increase compared to B6J wildtype mice, yet no sex differences were observed. (J,K) TPM values for Thy1 expression in micro-dissected hippocampal lysates demonstrate higher Thy1 expression in 4-, 12-, and 18-month-old 3xTg-AD mice. (L,M) TPM values for Thy1 expression in micro-dissected hippocampal lysates display a similar increase in Thy1 expression compared to B6J wildtype controls with no sex differences within groups. (N,O) Quantification of neurofilament-light chain (NfL) levels of plasma from 3xTg-AD and 5xFAD using Mesoscale Singleplex technology demonstrated an age-related increase in 3xTg-AD mice at only the 18-month timepoint (N), while age-related increases were found in 5xFAD mice at both 12-month and 18-month timepoints (O). n = 5–10 mice per genotype/age/sex. Data are represented as mean ± SEM. *p ≤ 0.05, ^**p ≤ 0.01, ^***p ≤ 0.001, ^****p ≤ 0.0001.