Fig. 1

Deregulated miRNAs in hippocampus of APPtg and TAUtg mice and human AD patients. a) Experimental design for sequencing using n = 12 per experimental group. b) Explanation of the 2 × 2 linear model, where those cells labeled with 1 are compared to the cells labeled with 0. In the age comparison, miRNA expression in all 10 month old (M) mice is compared to all 4 M mice. In the genotype comparison, miRNA expression in all transgenic (TG) mice is compared to all wild-type (WT) mice. In the age*genotype comparison, we assess which miRNAs are differentially expressed in the 10 M TG mice compared to all other groups. c) The 8 selected miRNAs that became significantly deregulated (FDR-corrected p-value< 0.05) in the miRNAseq experiment with increasing pathology and cognitive impairment (age*genotype effect) in APPtg and TAUtg mice combined with more than 20% change. d) Validation of 8 deregulated miRNAs in a new cohort of APPtg and APPwt mice at 4 M and 10 M using qPCR (n = 7–9/group), expressed relatively to the 4 M WT mice. Significant age*genotype interaction effects were found for miR-142a-, miR-146a-, miR-155-, miR-211- and miR-455-5p, with the 10M TG mice being significantly different from the other 3 groups in Tukey’s post hoc test (**, p < 0.01; ***, p < 0.001). For miR-10a, significant main effects for age and genotype were found, but no significant age*genotype interaction. miR-451a and miR-301b-3p remained unchanged. e) qPCR expression of the 6 validated miRNAs in hippocampus of AD patients and non-demented (ND) controls, demonstrating significant differences for hsa-miR-142-, −miR-146a-, −miR-155- and -miR-455-5p, whereas hsa-miR-10a-5p was too lowly expressed for qPCR assessment (t-test with Benjamini-Hochberg p-value adjustment; *, p < 0.05; ***, p < 0.001)