title: Plasma microRNA biomarker detection for mild cognitive impairment using differential correlation analysis.
abstract: BACKGROUND
  Mild cognitive impairment (MCI) is an intermediate state between normal aging and dementia including Alzheimer's disease. Early detection of dementia, and MCI, is a crucial issue in terms of secondary prevention. Blood biomarker detection is a possible way for early detection of MCI. Although disease biomarkers are detected by, in general, using single molecular analysis such as t-test, another possible approach is based on interaction between molecules.
  
  
  RESULTS
  Differential correlation analysis, which detects difference on correlation of two variables in case/control study, was carried out to plasma microRNA (miRNA) expression profiles of 30 age- and race-matched controls and 23 Japanese MCI patients. The 20 pairs of miRNAs, which consist of 20 miRNAs, were selected as MCI markers. Two pairs of miRNAs (hsa-miR-191 and hsa-miR-101, and hsa-miR-103 and hsa-miR-222) out of 20 attained the highest area under the curve (AUC) value of 0.962 for MCI detection. Other two miRNA pairs that include hsa-miR-191 and hsa-miR-125b also attained high AUC value of ≥ 0.95. Pathway analysis was performed to the MCI markers for further understanding of biological implications. As a result, collapsed correlation on hsa-miR-191 and emerged correlation on hsa-miR-125b might have key role in MCI and dementia progression.
  
  
  CONCLUSIONS
  Differential correlation analysis, a bioinformatics tool to elucidate complicated and interdependent biological systems behind diseases, detects effective MCI markers that cannot be found by single molecule analysis such as t-test.
authors.affiliation: Research Center for Global Agromedicine, Obihiro University of Agriculture and Veterinary Medicine, Obihiro, Hokkaido, Japan ; Medical Genome Center, National Center for Geriatrics and Gerontology, Obu, Aichi, Japan.
authors.forename: Mitsunori
authors.identifier: 0000-0001-5969-4068
authors.initials: M
authors.lastname: Kayano
authors.affiliation: Medical Genome Center, National Center for Geriatrics and Gerontology, Obu, Aichi, Japan.
authors.forename: Sayuri
authors.initials: S
authors.lastname: Higaki
authors.affiliation: Department of Bioinformatics and Molecular Neuropathology, Meiji Pharmaceutical University, Kiyose, Tokyo, Japan.
authors.forename: Jun-Ichi
authors.initials: JI
authors.lastname: Satoh
authors.affiliation: Department of Allergy and Clinical Immunology, National Center for Child Health and Development, Setagaya, Tokyo, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Matsumoto
authors.affiliation: Department of Neurology, Hirosaki University Graduate School of Medicine, Hirosaki, Aomori, Japan ; Department of Neurology, Oita University Faculty of Medicine, Yufu, Oita, Japan.
authors.forename: Etsuro
authors.initials: E
authors.lastname: Matsubara
authors.affiliation: Innovation Center for Clinical Research, National Center for Geriatrics and Gerontology, Obu, Aichi, Japan.
authors.forename: Osamu
authors.initials: O
authors.lastname: Takikawa
authors.affiliation: Medical Genome Center, National Center for Geriatrics and Gerontology, Obu, Aichi, Japan.
authors.forename: Shumpei
authors.initials: S
authors.lastname: Niida
keywords: Alzheimer’s disease; Coexpression; Dementia; Molecular network