Inflammation-Related microRNAs-146a and -155 Are Upregulated in Mild Cognitive Impairment Subjects Among Older Age Population in Montenegro

J Alzheimers Dis. 2022;90(2):625-638. doi: 10.3233/JAD-220676.

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; miR-146a; miR-155; mild cognitive impairment; neuroinflammation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Alzheimer Disease* / diagnosis
  • Alzheimer Disease* / genetics
  • Alzheimer Disease* / metabolism
  • Biomarkers
  • Cognitive Dysfunction* / diagnosis
  • Cognitive Dysfunction* / genetics
  • Humans
  • Inflammation / genetics
  • MicroRNAs* / metabolism
  • Montenegro

Substances

  • Biomarkers
  • MicroRNAs
  • MIRN146 microRNA, human
  • MIRN155 microRNA, human