Micro‐RNA dysregulation in brains of Alzheimer’s disease mice models: A systematic review

Abstract

AbstractBackgroundSeveral dysregulated miRNAs have been reported in Alzheimer’s disease mice models. However, not all may be relevant for human cases. Therefore, a compilation and evaluation of the evidence is required, before choosing miRNAs as biomarker candidates or treatment targets.MethodThe current review is being done following PRISMA guidelines. The search in MEDLINE yielded 3952 results. After “abstract and title screening”, 319 articles passed to “full text” screening. Currently, 139 studies are being reviewed, evaluating mice model, dysregulated miRNA, brain region, miRNA extraction and analysis method, and their predicted/proven targets. Only peer review articles of in vivo mice models are being included.ResultThis is an ongoing review and the first one of its nature. From a total of 90 different dysregulated miRNAs, 4 are the most consistent in the literature: miR‐146a, miR‐181, miR‐155 and miR‐200. The expression of miR‐146 is upregulated in the hippocampus of amyloid beta (5XFAD, APPswe/PS1L166P, APPswe/PSEN1dE9) and tau models (Tau22 and 3xTg‐AD for both of them). In general, this dysregulation is observed since early stages (3‐4 months) in transgenic mice, but also in 16.6 months‐old WT animals (1‐5). Parallelly, 2 studies confirmed increased levels of miR‐146 in the blood of MCI patients and in the hippocampus of AD patients (2,4). miR ‐155 is consistently upregulated in the hippocampus and cortex of APP and tau transgenic models, as well in AD patients (3,4,6). miR‐181a is overexpressed in the hippocampus of transgenic and old WT mice (2,7), whereas miR‐181c is downregulated in the APP/PS1 and SAMP8 mice (8,9). Finally, miR‐200 is downregulated in the hippocampus of 3‐9 months‐old APP/PS1 and SAMP8 mice (10,11), while an upregulation was observed in 10 months‐old Tg2576 mice (12). All of these studies validated their results with qRT‐PCR.ConclusionmiR‐146, miR‐181a and miR‐155 are consistently upregulated, whereas miR‐181c and miR‐200 are downregulated in the brains of different transgenic and non transgenic AD mice models at different ages. This data suggest further studies of these candidates miRNAs, as they are validated in human samples as well. However, a more robust conclusion can be made after assessing all the reported miRNAs.