title: Prognostic serum miRNA biomarkers associated with Alzheimer's disease shows concordance with neuropsychological and neuroimaging assessment.
abstract: There is no consensus for a blood-based test for the early diagnosis of Alzheimer's disease (AD). Expression profiling of small non-coding RNA's, microRNA (miRNA), has revealed diagnostic potential in human diseases. Circulating miRNA are found in small vesicles known as exosomes within biological fluids such as human serum. The aim of this work was to determine a set of differential exosomal miRNA biomarkers between healthy and AD patients, which may aid in diagnosis. Using next-generation deep sequencing, we profiled exosomal miRNA from serum (N=49) collected from the Australian Imaging, Biomarkers and Lifestyle Flagship Study (AIBL). Sequencing results were validated using quantitative reverse transcription PCR (qRT-PCR; N=60), with predictions performed using the Random Forest method. Additional risk factors collected during the 4.5-year AIBL Study including clinical, medical and cognitive assessments, and amyloid neuroimaging with positron emission tomography were assessed. An AD-specific 16-miRNA signature was selected and adding established risk factors including age, sex and apolipoprotein ɛ4 (APOE ɛ4) allele status to the panel of deregulated miRNA resulted in a sensitivity and specificity of 87% and 77%, respectively, for predicting AD. Furthermore, amyloid neuroimaging information for those healthy control subjects incorrectly classified with AD-suggested progression in these participants towards AD. These data suggest that an exosomal miRNA signature may have potential to be developed as a suitable peripheral screening tool for AD.
authors.affiliation: Department of Biochemistry and Molecular Biology, The University of Melbourne, Melbourne, VIC, Australia.|Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Melbourne, VIC, Australia.
authors.forename: L
authors.initials: L
authors.lastname: Cheng
authors.affiliation: CSIRO Digital Productivity Flagship/The Australian E-Health Research Centre, Herston, QLD, Australia.|CSIRO Food and Nutrition Flagship, Melbourne, VIC, Australia.
authors.forename: J D
authors.initials: JD
authors.lastname: Doecke
authors.affiliation: Department of Biochemistry and Molecular Biology, The University of Melbourne, Melbourne, VIC, Australia.|Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Melbourne, VIC, Australia.
authors.forename: R A
authors.initials: RA
authors.lastname: Sharples
authors.affiliation: Department of Nuclear Medicine and Centre for PET, Austin Health, Melbourne, VIC, Australia.|Department of Medicine, Austin Health, Melbourne, VIC, Australia.|Florey Institute, Melbourne, VIC, Australia.
authors.forename: V L
authors.initials: VL
authors.lastname: Villemagne
authors.affiliation: Florey Institute, Melbourne, VIC, Australia.
authors.forename: C J
authors.initials: CJ
authors.lastname: Fowler
authors.affiliation: Florey Institute, Melbourne, VIC, Australia.
authors.forename: A
authors.initials: A
authors.lastname: Rembach
authors.affiliation: Faculty of Computing Health and Science, Centre of Excellence for Alzheimer's Disease Research and Care, School of Medical Sciences, Edith Cowan University, Joondalup, WA, Australia.
authors.forename: R N
authors.initials: RN
authors.lastname: Martins
authors.affiliation: Department of Nuclear Medicine and Centre for PET, Austin Health, Melbourne, VIC, Australia.|Department of Medicine, Austin Health, Melbourne, VIC, Australia.
authors.forename: C C
authors.initials: CC
authors.lastname: Rowe
authors.affiliation: CSIRO Food and Nutrition Flagship, Melbourne, VIC, Australia.
authors.forename: S L
authors.initials: SL
authors.lastname: Macaulay
authors.affiliation: Florey Institute, Melbourne, VIC, Australia.
authors.forename: C L
authors.initials: CL
authors.lastname: Masters
authors.affiliation: Department of Biochemistry and Molecular Biology, The University of Melbourne, Melbourne, VIC, Australia.|Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Melbourne, VIC, Australia.
authors.forename: A F
authors.initials: AF
authors.lastname: Hill
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000097:blood* / Q000175:diagnosis / Q000235:genetics*; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D055354:Exosomes / Q000235:genetics; D005260:Female; D005820:Genetic Testing; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000097:blood*; D059906:Neuroimaging / Q000379:methods; D009483:Neuropsychological Tests; D011379:Prognosis; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D017423:Sequence Analysis, RNA; D059467:Transcriptome
chemical_list: D015415:Biomarkers; D035683:MicroRNAs