Profile of 6 microRNA in blood plasma distinguish early stage Alzheimer's disease patients from non-demented subjects.
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).
Laboratory of Preclinical Testing of Higher Standard, Nencki Institute of Experimental Biology of Polish Academy of Sciences, Warsaw, Poland.
Siranjeevi
S
Nagaraj
Laboratory of Preclinical Testing of Higher Standard, Nencki Institute of Experimental Biology of Polish Academy of Sciences, Warsaw, Poland.
Katarzyna
K
Laskowska-Kaszub
Laboratory of Bioinformatics, Nencki Institute of Experimental Biology of Polish Academy of Sciences, Warsaw, Poland.
Konrad J
KJ
Dębski
Laboratory of Preclinical Testing of Higher Standard, Nencki Institute of Experimental Biology of Polish Academy of Sciences, Warsaw, Poland.
Joanna
J
Wojsiat
Laboratory of Bioinformatics, Nencki Institute of Experimental Biology of Polish Academy of Sciences, Warsaw, Poland.
Michał
M
Dąbrowski
Department of Neurodegenerative Disorders, Mossakowski Medical Research Center, Warsaw, Poland.
Tomasz
T
Gabryelewicz
Laboratory of Neurodegeneration, International Institute of Molecular and Cell Biology, Warsaw, Poland.
Jacek
J
Kuźnicki
Laboratory of Preclinical Testing of Higher Standard, Nencki Institute of Experimental Biology of Polish Academy of Sciences, Warsaw, Poland.
Urszula
U
Wojda
D000368:Aged; D000544:Alzheimer Disease / Q000097:blood / Q000175:diagnosis / Q000235:genetics*; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid; D015415:Biomarkers / Q000097:blood / Q000134:cerebrospinal fluid; D003704:Dementia / Q000097:blood / Q000175:diagnosis / Q000235:genetics*; D003937:Diagnosis, Differential; D042241:Early Diagnosis; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods*; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000097:blood / Q000235:genetics*; D008875:Middle Aged; D010446:Peptide Fragments / Q000134:cerebrospinal fluid; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016875:tau Proteins / Q000134:cerebrospinal fluid
D016229:Amyloid beta-Peptides; D015415:Biomarkers; C555159:MIRN142 microRNA, human; C533896:MIRN200 microRNA, human; C546086:MIRN30b microRNA, human; C548912:MIRN483 microRNA, human; C560945:MIRN486 microRNA, human; C545730:MIRN502 microRNA, human; D035683:MicroRNAs; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D016875:tau Proteins
Alzheimer`s disease; Gerotarget; biomarker; early Alzheimer’s disease; microRNA; mild cognitive impairment