Research Papers: Gerotarget (Focus on Aging):
Profile of 6 microRNA in blood plasma distinguish early stage Alzheimer’s disease patients from non-demented subjects
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Siranjeevi Nagaraj1,*, Katarzyna Laskowska-Kaszub1,*, Konrad J. Dębski2, Joanna Wojsiat1, Michał Dąbrowski2, Tomasz Gabryelewicz3, Jacek Kuźnicki4 and Urszula Wojda1
1 Laboratory of Preclinical Testing of Higher Standard, Nencki Institute of Experimental Biology of Polish Academy of Sciences, Warsaw, Poland
2 Laboratory of Bioinformatics, Nencki Institute of Experimental Biology of Polish Academy of Sciences, Warsaw, Poland
3 Department of Neurodegenerative Disorders, Mossakowski Medical Research Center, Warsaw, Poland
4 Laboratory of Neurodegeneration, International Institute of Molecular and Cell Biology, Warsaw, Poland
* These authors have contributed equally to this work
Urszula Wojda, email:
Keywords: Alzheimer`s disease, early Alzheimer’s disease, mild cognitive impairment, microRNA, biomarker, Gerotarget
Received: October 07, 2016 Accepted: January 16, 2017 Published: February 05, 2017
Alzheimer’s disease (AD) is the most common age-related dementia. Among its major challenges is identifying molecular signatures characteristic for the early AD stage in patients with Mild Cognitive Impairment (MCI-AD), which could serve for deciphering the AD pathomechanism and also as non-invasive, easy-to-access biomarkers. Using qRT-PCR we compared the microRNA (miRNA) profiles in blood plasma of 15 MCI-AD patients, whose diagnoses were confirmed by cerebrospinal fluid (CSF) biomarkers, with 20 AD patients and 15 non-demented, age-matched individuals (CTR).
To minimize methodological variability, we adhered to standardization of blood and CSF assays recommended by the international Joint Programming for Neurodegenerative Diseases (JPND) BIOMARKAPD consortium, and we employed commercially available Exiqon qRT-PCR-assays. In the first screening, we assessed 179 miRNAs of plasma. We confirmed 23 miRNAs reported earlier as AD biomarker candidates in blood and found 26 novel differential miRNAs between AD and control subjects. For representative 15 differential miRNAs, the TargetScan, MirTarBase and KEGG database analysis indicated putative protein targets among such AD hallmarks as MAPT (Tau), proteins involved in amyloidogenic proteolysis, and in apoptosis. These 15 miRNAs were verified in separate, subsequent subject groups. Finally, 6 miRNAs (3 not yet reported in AD context and 3 reported in AD blood) were selected as the most promising biomarker candidates differentiating early AD from controls with the highest fold changes (from 1.32 to 14.72), consistent significance, specificities from 0.78 to 1 and sensitivities from 0.75 to 1. (patent pending, PCT/IB2016/052440).
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