Fig. 3.

Loss of Tet1 Increases AD-associated Pathology in 5×FAD Mice.

A) Results from the forced-swim assay (FST). We measured a significant difference in immobility between 5×FAD (n = 14) mice relative to WT (n = 18; p < 0.0001) and Tet1^(+/−) (n = 9; p < 0.0001) mice relative to 5xFAD/Tet1^(+/−) (n = 10; p < 0.0001). A near significant difference between 5xFAD and 5xFAD/Tet1^(+/−) was measured (p = 0.0637); two-tailed unpaired t-test. B) The TST identified significant performances between the WT (n = 18) and Tet1^(+/−) (n = 9; p = 0.0397) and 5xFAD/Tet1^(+/−) (n = 9; p = 0.0434) mice; two-tailed unpaired t-test. C) The fear cue portion of the fear conditioning assay found no significant difference in fear memory between conditions across the total time (p = 0.54; two-way RM ANOVA) and their performance normalized for baseline freezing behavior, but a non-significant towards reduced cognition was noted between 5xFAD (n = 15; p = 0.2178; two-tailed unpaired t-test) and 5xFAD/Tet1^(+/−) (n = 10; p = 0.1055; two-tailed unpaired t-test) mice relative to WT (n = 18). The performance between 5xFAD/Tet1^(+/−) relative to 5xFAD is not significantly different. D) Anti-Aβ42 staining in mouse brain (2.5x magnification). The image brightness and contrast were adjusted to improve visibility for the image sections displayed in this figure. Using raw, unprocessed image files, the plaque burden was calculated with the STARDIST machine learning algorithm and identified a significant difference in Aβ42 abundance between 5xFAD (n = 3) and 5xFAD/Tet1^(+/−) (n = 3) mice (p = 0.044; two-tailed nested t-test). Error bars indicate mean ± SD; **** p < 0.0001, *** p = 0.0001–0.001, ** p = 0.001–0.01, ** p = 0.01–0.05, ns p ≥ 0.05.