Study of microRNAs and their targets in exosome from Alzheimer’s and Frontotemporal Dementia patients

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Abstract Background A central role of RNA metabolism and non‐coding RNAs biogenesis has emerged in Alzheimer’s disease (AD) and Frontotemporal Dementia (FTD). We investigated miRNA cargo of Small Extracellular Vesicles (SEVs) derived from plasma of FTD and AD patients, and Healthy Controls (HC). The purpose was to evaluate deregulated miRNAs in patients to identify new peripheral biomarkers and to determine mRNA targets involved in FTD and AD pathogenesis. Method SEVs were isolated from plasma of 13 FTD patients, 20 AD and 20 HC by differential centrifugation and characterized by Nanosight and Western Blot. MicroRNA libraries were generated using Small RNA Seq Library Prep Kit (Lexogen) and sequenced on a NextSeq 500 (Illumina). Interaction prediction was carried out on TarBase v.8 database. Result We found a total of 339 Differentially Expressed (DE) microRNAs in FTD, and 291 DE microRNAs in AD compared to controls. Interestingly, 74 miRNAs were commonly deregulated: 38 had the same trend and 36 had an opposite trend. In order to find a miRNA biomarker able to discern FTD and AD, we selected 8 DE miRNAs with opposite trend based on fold changes difference and targets. In fact these miRNAs were found to have validated mRNAs target that may be of interest for molecular study of dementia, such as APP and PTEN. Conclusion Our data highlight the importance of miRNAs cargo examination in EVs of FTD and AD patients. In fact, their potential is exploitable both for biomarkers discovery and for study of gene expression alteration in dementia pathogenesis.

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