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A combined miRNA-piRNA signature to detect Alzheimer's disease

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Item Type:Article
Title:A combined miRNA-piRNA signature to detect Alzheimer's disease
Creators Name:Jain, G. and Stuendl, A. and Rao, P. and Berulava, T. and Pena Centeno, T. and Kaurani, L. and Burkhardt, S. and Delalle, I. and Kornhuber, J. and Hüll, M. and Maier, W. and Peters, O. and Esselmann, H. and Schulte, C. and Deuschle, C. and Synofzik, M. and Wiltfang, J. and Mollenhauer, B. and Maetzler, W. and Schneider, A. and Fischer, A.
Abstract:Alzheimer's disease (AD) is the most common neurodegenerative disorder causing huge emotional and economic burden to our societies. An effective therapy has not been implicated yet, which is in part also due to the fact that pathological changes occur years before clinical symptoms manifest. Thus, there is a great need for the development of a translatable biomarker. Recent evidence highlights microRNAs as candidate biomarkers. In this study, we use next-generation sequencing to study the small noncoding RNAome (sncRNAome) in exosomes derived from human cerebrospinal fluid (CSF). We show that the sncRNAome from CSF-derived exosomes is dominated not only by microRNAs (miRNAs) but also by PIWI-interacting RNAs (piRNAs). We define a combined signature consisting of three miRNAs and three piRNAs that are suitable to detect AD with an AUC of 0.83 in a replication cohort and furthermore predict the conversion of mild-cognitive impaired (MCI) patients to AD dementia with an AUC of 0.86 for the piRNA signature. When combining the smallRNA signature with pTau and Aβ 42/40 ratio the AUC reaches 0.98. Our study reports a novel exosomal small noncoding RNA signature to detect AD pathology and provides the first evidence that in addition to miRNAs, piRNAs should also be considered as a candidate biomarker for AD.
Keywords:Alzheimer Disease, Amyloid beta-Peptides, Area Under Curve, Biomarkers, Cognitive Dysfunction, Cohort Studies, Germany, MicroRNAs, Peptide Fragments, Small Interfering RNA
Source:Translational Psychiatry
Publisher:Nature Publishing Group
Page Range:250
Date:7 October 2019
Official Publication:https://doi.org/10.1038/s41398-019-0579-2
PubMed:View item in PubMed

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