Open Access Highly Accessed Research

A blood based 12-miRNA signature of Alzheimer disease patients

Petra Leidinger1, Christina Backes1, Stephanie Deutscher1, Katja Schmitt1, Sabine C Mueller1, Karen Frese2, Jan Haas2, Klemens Ruprecht3, Friedemann Paul34, Cord Stähler5, Christoph JG Lang6, Benjamin Meder2, Tamas Bartfai7, Eckart Meese1 and Andreas Keller15*

Author Affiliations

1 Department of Human Genetics, Saarland University, Kirrbergerstraße, Building 60, 66421 Homburg, Germany

2 Internal Medicine II, Heidelberg University, Im Neuenheimer Feld 350, 69120 Heidelberg, Germany

3 Clinical and Experimental Multiple Sclerosis Research Center, Charité - University Medicine Berlin, Campus Mitte, Charitéplatz 1, 10117 Berlin, Germany

4 NeuroCure Clinical Research Center, Charité - University Medicine Berlin, Campus Mitte, Charitéplatz 1,10117 Berlin, Germany

5 Siemens Healthcare, Strategy, Hartmannstr. 16, 91052 Erlangen, Germany

6 Neurological Unit, University of Erlangen, Schwabachanlage 6, 91054 Erlangen, Germany

7 Department of Chemical Physiology, The Scripps Research Institute, 10550 N Torrey Pines Rd, La Jolla, CA 92037, USA

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Genome Biology 2013, 14:R78  doi:10.1186/gb-2013-14-7-r78

Published: 29 July 2013

Abstract

Background

Alzheimer disease (AD) is the most common form of dementia but the identification of reliable, early and non-invasive biomarkers remains a major challenge. We present a novel miRNA-based signature for detecting AD from blood samples.

Results

We apply next-generation sequencing to miRNAs from blood samples of 48 AD patients and 22 unaffected controls, yielding a total of 140 unique mature miRNAs with significantly changed expression levels. Of these, 82 have higher and 58 have lower abundance in AD patient samples. We selected a panel of 12 miRNAs for an RT-qPCR analysis on a larger cohort of 202 samples, comprising not only AD patients and healthy controls but also patients with other CNS illnesses. These included mild cognitive impairment, which is assumed to represent a transitional period before the development of AD, as well as multiple sclerosis, Parkinson disease, major depression, bipolar disorder and schizophrenia. miRNA target enrichment analysis of the selected 12 miRNAs indicates an involvement of miRNAs in nervous system development, neuron projection, neuron projection development and neuron projection morphogenesis. Using this 12-miRNA signature, we differentiate between AD and controls with an accuracy of 93%, a specificity of 95% and a sensitivity of 92%. The differentiation of AD from other neurological diseases is possible with accuracies between 74% and 78%. The differentiation of the other CNS disorders from controls yields even higher accuracies.

Conclusions

The data indicate that deregulated miRNAs in blood might be used as biomarkers in the diagnosis of AD or other neurological diseases.

Keywords:
Alzheimer disease; miRNA; biomarker; next-generation sequencing; quantitative Real Time PCR