Andreas Keller1, Christina Backes2, Jan Haas3, Petra Leidinger4, Walter Maetzler5, Christian Deuschle5, Daniela Berg5, Christoph Ruschil5, Valentina Galata2, Klemens Ruprecht6, Cord Stähler7, Maximilian Würstle7, Daniel Sickert7, Manfred Gogol8, Benjamin Meder3, Eckart Meese4. 1. Clinical Bioinformatics, Saarland University, Saarbrücken, Germany. Electronic address: andreas.keller@ccb.uni-saarland.de. 2. Clinical Bioinformatics, Saarland University, Saarbrücken, Germany. 3. Internal Medicine, Heidelberg University, Heidelberg, Germany. 4. Department for Human Genetics, Saarland University Hospital, Homburg, Germany. 5. Department of Neurodegeneration and Hertie-Institute of Clinical Brain Research of the Eberhard-Karls-University, German Center for Neurodegenerative Diseases, Tübingen, Germany. 6. Department of Neurology, Charité - Universitätsmedizin Berlin, Berlin, Germany. 7. Siemens Healthcare, Erlangen, Germany. 8. Krankenhaus Lindenbrunn, Lindenbrunn, Germany.
Abstract
INTRODUCTION: Molecular biomarkers for Alzheimer's disease (AD) can support detection and improved care for patients, but novel candidates require verification. We previously reported a 12-micro RNA (miRNA) blood-based signature using next-generation sequencing (NGS) of 54 AD cases and 22 controls. METHODS: We performed validation of 49 AD cases and 55 controls using NGS and also included 20 mild cognitive impairment and 90 multiple sclerosis samples to identify nonspecific markers. Thus, 103 AD cases, 77 unaffected controls, and 110 diseased controls were sequenced. Although the initial cohort came predominantly from the United States, the validation samples were collected in Germany. RESULTS: Five hundred eighty miRNAs were detected in the blood. In the initial cohort, we observed 203, in the validation cohort, 146 dysregulated miRNAs at a significance level of 0.05. With 68 miRNAs, the overlap was significant (P = .0003). Likewise, the area under the receiver operator characteristic curve values of the miRNAs correlated (correlation of 0.93; 95% confidence interval 0.89-0.96; P <10(-16)). DISCUSSION: MiRNAs have the potential to support AD diagnosis and patient care.
INTRODUCTION: Molecular biomarkers for Alzheimer's disease (AD) can support detection and improved care for patients, but novel candidates require verification. We previously reported a 12-micro RNA (miRNA) blood-based signature using next-generation sequencing (NGS) of 54 AD cases and 22 controls. METHODS: We performed validation of 49 AD cases and 55 controls using NGS and also included 20 mild cognitive impairment and 90 multiple sclerosis samples to identify nonspecific markers. Thus, 103 AD cases, 77 unaffected controls, and 110 diseased controls were sequenced. Although the initial cohort came predominantly from the United States, the validation samples were collected in Germany. RESULTS: Five hundred eighty miRNAs were detected in the blood. In the initial cohort, we observed 203, in the validation cohort, 146 dysregulated miRNAs at a significance level of 0.05. With 68 miRNAs, the overlap was significant (P = .0003). Likewise, the area under the receiver operator characteristic curve values of the miRNAs correlated (correlation of 0.93; 95% confidence interval 0.89-0.96; P <10(-16)). DISCUSSION: MiRNAs have the potential to support AD diagnosis and patient care.
Authors: Tobias Fehlmann; Christina Backes; Marcello Pirritano; Thomas Laufer; Valentina Galata; Fabian Kern; Mustafa Kahraman; Gilles Gasparoni; Nicole Ludwig; Hans-Peter Lenhof; Henrike A Gregersen; Richard Francke; Eckart Meese; Martin Simon; Andreas Keller Journal: Nucleic Acids Res Date: 2019-05-21 Impact factor: 16.971
Authors: Nicole Ludwig; Anne Hecksteden; Mustafa Kahraman; Tobias Fehlmann; Thomas Laufer; Fabian Kern; Tim Meyer; Eckart Meese; Andreas Keller; Christina Backes Journal: RNA Biol Date: 2019-05-10 Impact factor: 4.652
Authors: Tobias Fehlmann; Christina Backes; Mustafa Kahraman; Jan Haas; Nicole Ludwig; Andreas E Posch; Maximilian L Würstle; Matthias Hübenthal; Andre Franke; Benjamin Meder; Eckart Meese; Andreas Keller Journal: Nucleic Acids Res Date: 2017-09-06 Impact factor: 16.971
Authors: Julia Alles; Tobias Fehlmann; Ulrike Fischer; Christina Backes; Valentina Galata; Marie Minet; Martin Hart; Masood Abu-Halima; Friedrich A Grässer; Hans-Peter Lenhof; Andreas Keller; Eckart Meese Journal: Nucleic Acids Res Date: 2019-04-23 Impact factor: 16.971
Authors: Harald Hampel; Sid E O'Bryant; José L Molinuevo; Henrik Zetterberg; Colin L Masters; Simone Lista; Steven J Kiddle; Richard Batrla; Kaj Blennow Journal: Nat Rev Neurol Date: 2018-11 Impact factor: 42.937