title: A blood based 12-miRNA signature of Alzheimer disease patients.
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.
authors.forename: Petra
authors.initials: P
authors.lastname: Leidinger
authors.forename: Christina
authors.initials: C
authors.lastname: Backes
authors.forename: Stephanie
authors.initials: S
authors.lastname: Deutscher
authors.forename: Katja
authors.initials: K
authors.lastname: Schmitt
authors.forename: Sabine C
authors.initials: SC
authors.lastname: Mueller
authors.forename: Karen
authors.initials: K
authors.lastname: Frese
authors.forename: Jan
authors.initials: J
authors.lastname: Haas
authors.forename: Klemens
authors.initials: K
authors.lastname: Ruprecht
authors.forename: Friedemann
authors.initials: F
authors.lastname: Paul
authors.forename: Cord
authors.initials: C
authors.lastname: Stähler
authors.forename: Christoph J G
authors.initials: CJ
authors.lastname: Lang
authors.forename: Benjamin
authors.initials: B
authors.lastname: Meder
authors.forename: Tamas
authors.initials: T
authors.lastname: Bartfai
authors.forename: Eckart
authors.initials: E
authors.lastname: Meese
authors.forename: Andreas
authors.initials: A
authors.lastname: Keller
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000097:blood* / Q000235:genetics*; D015415:Biomarkers / Q000097:blood; D001921:Brain / Q000378:metabolism; D016022:Case-Control Studies; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D035683:MicroRNAs / Q000097:blood* / Q000235:genetics*; D008875:Middle Aged; D060888:Real-Time Polymerase Chain Reaction; D015203:Reproducibility of Results
chemical_list: D015415:Biomarkers; D035683:MicroRNAs
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