Evaluation of the Serum Dkk-1, Tenascin-C, Oxidative Stress Markers Levels and Wnt Signaling Pathway Genes Expression in
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Evaluation of the Serum Dkk-1, Tenascin-C, Oxidative Stress Markers Levels and Wnt Signaling Pathway Genes Expression in Patients with Alzheimer’s Disease Zahra Hasanzadeh 1,2 & Alireza Nourazarian 1,2 Somayeh Sadrirad 2
&
Masoud Nikanfar 3 & Delara Laghousi 4 & Amir Mansour Vatankhah 1 &
Received: 29 June 2020 / Accepted: 9 September 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020
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 Oxidative stress . DKK-1 . TNC . Wnt signaling . Alzheimer's disease
Introduction Alzheimer’s disease (AD) is a globally predominant neurodegenerative disorder, associated with dementia, which is estimated to impact 115 million people worldwide by 2050 (Altuna-Azkargorta and Mendioroz-Iriarte 2020; Doecke et al. 2012; Lehmann and Teunissen 2016; Zetterberg 2017;
* Alireza Nourazarian [email protected]; [email protected] 1
Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
2
Department of Biochemistry and Clinical Laboratories, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
3
Department of Neurology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
4
Social Determinants of Health Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
Huynh and Mohan 2017). It has been established that neurofibrillary tangles (NFTs) and amyloid Beta (Aβ) plaques are the primary markers of AD, which mediate the gradual dysfunction of the neural network thereby, resulting in dementia (Thysiadis et al. 2016). Although numerous studies have explored underlying causes of AD in the l
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