title: Validating Alzheimer's disease micro RNAs using next-generation sequencing.
abstract: 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.
  
  
  
  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.
  
  
  
  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)).
  
  
  
  MiRNAs have the potential to support AD diagnosis and patient care.
authors.affiliation: Clinical Bioinformatics, Saarland University, Saarbrücken, Germany. Electronic address: andreas.keller@ccb.uni-saarland.de.
authors.forename: Andreas
authors.initials: A
authors.lastname: Keller
authors.affiliation: Clinical Bioinformatics, Saarland University, Saarbrücken, Germany.
authors.forename: Christina
authors.initials: C
authors.lastname: Backes
authors.affiliation: Internal Medicine, Heidelberg University, Heidelberg, Germany.
authors.forename: Jan
authors.initials: J
authors.lastname: Haas
authors.affiliation: Department for Human Genetics, Saarland University Hospital, Homburg, Germany.
authors.forename: Petra
authors.initials: P
authors.lastname: Leidinger
authors.affiliation: Department of Neurodegeneration and Hertie-Institute of Clinical Brain Research of the Eberhard-Karls-University, German Center for Neurodegenerative Diseases, Tübingen, Germany.
authors.forename: Walter
authors.initials: W
authors.lastname: Maetzler
authors.affiliation: Department of Neurodegeneration and Hertie-Institute of Clinical Brain Research of the Eberhard-Karls-University, German Center for Neurodegenerative Diseases, Tübingen, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Deuschle
authors.affiliation: Department of Neurodegeneration and Hertie-Institute of Clinical Brain Research of the Eberhard-Karls-University, German Center for Neurodegenerative Diseases, Tübingen, Germany.
authors.forename: Daniela
authors.initials: D
authors.lastname: Berg
authors.affiliation: Department of Neurodegeneration and Hertie-Institute of Clinical Brain Research of the Eberhard-Karls-University, German Center for Neurodegenerative Diseases, Tübingen, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Ruschil
authors.affiliation: Clinical Bioinformatics, Saarland University, Saarbrücken, Germany.
authors.forename: Valentina
authors.initials: V
authors.lastname: Galata
authors.affiliation: Department of Neurology, Charité - Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Klemens
authors.initials: K
authors.lastname: Ruprecht
authors.affiliation: Siemens Healthcare, Erlangen, Germany.
authors.forename: Cord
authors.initials: C
authors.lastname: Stähler
authors.affiliation: Siemens Healthcare, Erlangen, Germany.
authors.forename: Maximilian
authors.initials: M
authors.lastname: Würstle
authors.affiliation: Siemens Healthcare, Erlangen, Germany.
authors.forename: Daniel
authors.initials: D
authors.lastname: Sickert
authors.affiliation: Krankenhaus Lindenbrunn, Lindenbrunn, Germany.
authors.forename: Manfred
authors.initials: M
authors.lastname: Gogol
authors.affiliation: Internal Medicine, Heidelberg University, Heidelberg, Germany.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Meder
authors.affiliation: Department for Human Genetics, Saarland University Hospital, Homburg, Germany.
authors.forename: Eckart
authors.initials: E
authors.lastname: Meese
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000097:blood* / Q000235:genetics*; D015415:Biomarkers / Q000097:blood; D060825:Cognitive Dysfunction; D005260:Female; D005858:Germany; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000097:blood / Q000235:genetics*; D017421:Sequence Analysis / Q000379:methods*; D014481:United States; D015854:Up-Regulation
chemical_list: D015415:Biomarkers; D035683:MicroRNAs
keywords: Alzheimer's disease; Biomarker; Validation; miRNA