Deregulation of neuronal miRNAs induced by amyloid-β or TAU pathology

Despite diverging levels of amyloid-β (Aβ) and TAU pathology, different mouse models, as well as sporadic AD patients show predictable patterns of episodic memory loss. MiRNA deregulation is well established in AD brain but it is unclear whether Aβ or Tau pathology drives those alterations and whether miRNA changes contribute to cognitive decline. Therefore miRNAseq was performed on the hippocampus of APPswe/PS1L166P and Thy-TAU22 mice and their respective wild-type littermates when they were cognitively intact (4 months) and impaired (10 months). We found 6 miRNAs that are commonly upregulated between APPtg and TAUtg mice, and four of these were also altered in AD patients. All 6 miRNAs are strongly enriched in neurons as verified by in situ hybridization. miRNAseq on 96 biological samples (mouse hippocampus), n=12 per experimental group, examining APPswe/PSEN1L166P and Thy-TAU22 mice and their respective WT littermates, at 4 and 10 months of age (8 groups in total)