Evaluation of the Serum Dkk-1, Tenascin-C, Oxidative Stress Markers Levels and Wnt Signaling Pathway Genes Expression in Patients with Alzheimer's Disease

J Mol Neurosci. 2021 Apr;71(4):879-887. doi: 10.1007/s12031-020-01710-9. Epub 2020 Sep 15.

Abstract

Early diagnosis of Alzheimer's disease (AD) using potential biomarkers may help with implementing early therapeutic interventions, monitoring, and ultimately disease treatment. The current study aimed to evaluate serum levels of DKK-1, TNC, and oxidative stress markers, as well as analyzing the expression of LRP6, GSK3A, and GSK3B genes in patients with AD. Serum levels of DKK-1, TNC, TOS, TAC, and MDA were measured in 40 AD patients and 40 healthy individuals. Additionally, the relative expressions of LRP6, GSK3A, and GSK3B genes in whole blood were evaluated. Receiver operating characteristic (ROC) analysis was used to investigate the incremental diagnostic value of each factor in the study groups. Mean serum levels of DKK-1, TNC, TOS, TAC, and MDA were significantly higher in the AD group compared to the healthy group (p < 0.001). Moreover, a significant difference was observed in the expression of LRP6 and GSK3A genes (p < 0.001) between patients and healthy groups. However, the expression of GSK3B did not significantly differ between the two groups (p > 0.05). With considerable sensitivity and specificity, ROC analysis demonstrated the diagnostic efficacy of DKK-1 and TNC serum levels in AD within an area under the ROC curve of ≥ 0.98 (p ˂ 0.001). The results showed that evaluating serum levels of DKK-1 and TNC, as well as assessing the expression of LRP6, could be utilized for diagnosis and monitoring of AD patients.

Keywords: Alzheimer's disease; DKK-1; Oxidative stress; TNC; Wnt signaling.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alzheimer Disease / blood*
  • Alzheimer Disease / diagnosis
  • Biomarkers / blood
  • Female
  • Glycogen Synthase Kinase 3 / blood
  • Humans
  • Intercellular Signaling Peptides and Proteins / blood*
  • Low Density Lipoprotein Receptor-Related Protein-6 / blood
  • Male
  • Malondialdehyde / blood
  • Middle Aged
  • Oxidative Stress*
  • Tenascin / blood*
  • Wnt Signaling Pathway*

Substances

  • Biomarkers
  • DKK1 protein, human
  • Intercellular Signaling Peptides and Proteins
  • LRP6 protein, human
  • Low Density Lipoprotein Receptor-Related Protein-6
  • TNC protein, human
  • Tenascin
  • Malondialdehyde
  • Glycogen Synthase Kinase 3