Volume 11, Issue 3 (May & June 2020)                   BCN 2020, 11(3): 349-358 | Back to browse issues page

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Sedighi M, Baluchnejadmojarad T, Fallah S, Moradi N, Afshin-Majd S, Roghani M. The Association Between Circulating Klotho and Dipeptidyl Peptidase-4 Activity and Inflammatory Cytokines in Elderly Patients With Alzheimer Disease. BCN. 2020; 11 (3) :349-358
URL: http://bcn.iums.ac.ir/article-1-1459-en.html
1- Cellular and Molecular Research Center, Iran University of Medical Sciences, Tehran, Iran.
2- Department of Neuroscience, Faculty of Advanced Technologies in Medicine, Iran University of Medical Sciences, Tehran, Iran.
3- Department of Biochemistry, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.
4- Department of Clinical Biochemistry, Faculty of Medicine, Kurdistan University of Medical Sciences, Sanandaj, Iran.
5- Neurophysiology Research Center, Shahed University, Tehran, Iran.
Introduction: Klotho and dipeptidyl peptidase-4 (DPP4) are two proteins that modulate inflammatory pathways. We investigated the association between circulating klotho and DPP4 activity and their relationship with inflammatory cytokines, miR-29a, and miR-195 in Alzheimer disease (AD).
Methods: This study was conducted on 16 AD patients and 16 healthy age-matched controls. Plasma levels of tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β, interleukin-6 (IL-6), klotho, and DPP4 were measured by enzyme-linked immunosorbent assay. Plasma expression of miR-29a and miR-195 were also measured and compared by a real-time polymerase chain reaction.
Results: There was a significant increase in TNF-α (p=0.006), IL-1β (p=0.012), and IL-6 (p=0.012) levels in the AD subjects compared with controls. Also, we found a decrease in plasma levels of klotho and an increase in plasma levels of DPP4 in the AD group that was not significant compared with the controls. Lower expression of miR-29a (P=0.009) and higher expression of miR-195 (P=0.003) were observed in the AD group that was significant than controls. Further analysis showed a negative correlation between klotho and plasma levels of IL-6 (r=-0.58, p=0.01). Also, there was a positive correlation between plasma DPP4 activity and TNF-α levels (r=0.50, P=0.04) and IL-1β (r=0.62, P=0.01). Likewise, plasma klotho concentration showed a negative correlation with the age of AD subjects (r=-0.56, P=0.02).
Conclusion: TNF-α, IL-1β, and IL-6 are involved in AD pathophysiology, and dysregulation of DPP4 and klotho may be associated with the inflammatory response of AD. Down-regulation of miR-29a and up-regulation of miR‑195 indicated the role of miRNAs in the AD process.
Type of Study: Original | Subject: Cellular and molecular Neuroscience
Received: 2019/03/18 | Accepted: 2019/10/15 | Published: 2020/07/14

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