a, Tert mRNA levels in the cortex and hippocampus of 3xTg-AD and wildtype control (B6;129S) mice (n = 4, 3-month-old; nonTg vs. 3xTg-AD: p = 0.007, p = 0.0017, respectively, two-way ANOVA with Sidak’s multiple comparisons test). b, Tert mRNA levels in the cortex and hippocampus of 5xFAD and wildtype littermate control (B6;SJL) mice (n = 4, 2~3-month-old; nonTg vs. 5xFAD: p = 0.0001, p = 0.0074, respectively, two-way ANOVA with Sidak’s multiple comparisons test). c, Tert mRNA levels in primary neurons isolated from 3xTg-AD and control mice at DIV 14 (n = 3, p = 0.0089, two-tailed unpaired t-test). d, Tert mRNA levels in primary neurons isolated from 5xFAD and control mice at DIV 14 (n = 3, p = 0.0198, two-tailed unpaired t-test). e, Telomerase activity in cortical and hippocampal neurons isolated from 5xFAD and control mice (n = 4, 2~3-month-old; nonTg vs. 5xFAD: p = 0.0067, p = 0.0173, respectively, two-way ANOVA with Sidak’s multiple comparisons test). f, Representative view of H3K9me3 repressive histone mark occupancy in Tert gene of 5xFAD and control mouse primary neurons at DIV 14. g, mRNA levels of histone demethylase Kdm1a, Kdm4b, and Kdm4c genes in cortical and hippocampal neurons of 5xFAD and wildtype littermate control mice (n = 4, 2~3-month-old; p = 0.0178, p = 0.0094, p = 0.0289, respectively, two-tailed unpaired t-test). h, Representative images of KDM1A immunostaining in the CA1 hippocampal subfield of 5xFAD and wildtype littermate control mice (2~3-month-old). Experiments were repeated three times independently with similar results. Scale bar, 100 μm. i, Tert mRNA levels in the cortex and hippocampus of 5xFAD mice treated with chaetocin or BIX-01294 (n = 4, 2~3-month-old; DMSO vs. inhibitor: cortex: p = 0.0015, p = 0.0036, respectively, hippocampus: p < 0.0001, p < 0.0001, respectively, two-way ANOVA with Tukey’s multiple comparisons test). Data are mean ± s.e.m. *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001.