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Article type: Research Article
Authors: Rovčanin Dragović, Isidoraa; * | Popović, Natašaa | Ždralević, Mašaa | Radulović, Ljiljanab | Vuković, Tijanab | Marzano, Flavianac | Tullo, Apolloniac | Radunović, Miodraga
Affiliations: [a] University of Montenegro, Faculty of Medicine, Podgorica, Montenegro | [b] Clinical Center of Montenegro, Department of Neurology, Podgorica, Montenegro | [c] Institute of Biomembranes, Bioenergetics and Molecular Biotechnologies, National Research Council, CNR, Bari, Italy
Correspondence: [*] Correspondence to: Dr. Isidora Rovčanin Dragović, Faculty of Medicine, University of Montenegro, Kruševac bb, 81000 Podgorica, Montenegro. Tel.: +382 69 878 770; E-mail: [email protected].
Abstract: Background:Pathological and clinical features of Alzheimer’s disease (AD) are in temporal discrepancy and currently accepted clinical tests provide the diagnosis decades after the initial pathophysiological events. In order to enable a more timely detection of AD, research efforts are directed to identification of biomarkers of the early symptomatic stage. Neuroinflammatory signaling pathways and inflammation-related microRNAs (miRNAs) could possibly have a crucial role in AD, making them promising potential biomarkers. Objective:We examined the expression of circulatory miRNAs with a documented role in AD pathophysiology: miR-29a/b, miR-101, miR-125b, miR-146a, and miR-155 in the plasma of AD patients (AD, n = 12), people with mild cognitive impairment (MCI, n = 9), and normocognitive group (CTRL, n = 18). We hypothesized that these miRNA expression levels could correlate with the level of participants’ cognitive decline. Methods:The study participants completed the standardized interview, neurological examination, neuropsychological assessment, and biochemical analyses. miRNA expression levels were assessed by RT-PCR. Results:Neurological and laboratory findings could not account for MCI, but miR-146a and -155 were upregulated in the MCI group compared to the control. miR-146a, known to mediate early neuroinflammatory AD events, was also upregulated in the MCI compared to AD group. ROC curve analysis for miRNA-146a showed 77.8% sensitivity and 94.4% specificity and 66.7% sensitivity and 88.9% specificity for miR-155. Conclusion:Determination of circulatory inflamma-miRs-146a and -155 expression, together with neuropsychological screening, could become a non-invasive tool for detecting individuals with an increased risk for AD, but research on a larger cohort is warranted.
Keywords: Alzheimer’s disease, mild cognitive impairment, miR-146a, miR-155, neuroinflammation
DOI: 10.3233/JAD-220676
Journal: Journal of Alzheimer's Disease, vol. 90, no. 2, pp. 625-638, 2022
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