Circulating micrornas in blood as biomarkers of early Alzheimer’s disease
Among the major challenges related to Alzheimer’s disease (AD) is identifying biomarkers of the early AD stage in easily accessible blood samples, as an alternative to existing sophisticated (brain imaging) and invasive (cerebrospinal fluid, CSF) procedures for AD diagnosis. One of the promising approaches concentrates on circulating microRNAs (miRNAs). Using qRT-PCR we compared the miRNA profiles in the blood plasma of 15 mild cognitive impairment patients with early AD (MCI-AD), whose diagnoses were confirmed by CSF biomarkers, with 20 later AD patients and 15 non-demented, age-matched individuals (CTR). In the first screening, we assessed 179 plasma miRNAs. We confirmed 23 miRNAs reported earlier as AD biomarker candidates and found 26 novel differential miRNAs. For 15 statistically significant differential miRNAs, the TargetScan, MirTarBase and KEGG database analysis indicated putative targets among key proteins involved in AD pathology such as MAPT (tau), APP and enzymes of amyloidogenic proteolysis. These 15 miRNAs were verified in separate, subsequent AD, MCI-AD and CTR groups. Finally, 6 miRNAs 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). The identified miRNA panel in the blood could not only serve as an early non-invasive AD diagnostic, but could also indicate individualized therapy. FINANCIAL SUPPORT: This research was supported by the EU Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement no 665735 (Bio4Med) and by the funding from the Polish Ministry of Science and Higher Education (agreement no 3548/ H2020/COFUND/2016/2). The work was carried out with the use of CePT infrastructure financed by the European Regional Development Fund within the Operational Programme “Innovative economy” for 2007–2013.