Effect of Memantine on Expression of NAT-Rad18, Rad18 and Sorl1 Genes in Rat Model of Alzheimer's Disease

 Dysregulation of long-term expression of non-coding RNAs (lncRNAs) has a potential role in progressive brain disorders such as Alzheimer's disease. This study aimed to analyze the apoptosis and expression of 51A and NAT-Rad18 lncRNAs and their target genes in brain tissue and peripheral blood mononuclear cells (PBMCs) of the rat model of AD, before and after memantine treatment.

 Twenty-eight male Wistar rats were divided into four groups: 1. Normal control (n = 4), 2. Sham-operated (n = 4), 3. Alzheimer's control (n = 10), and 4. The experimental group (n = 10) was treated with memantine. The qPCR and TUNEL tests were used to detect the lncRNAs expression and apoptosis.

 Sorl1 gene was reduced in brain tissue of Alzheimer’s control (p = 0.016) and PBMCs of Alzheimer's control and experimental groups (p = 0.002 and p = 0.001 respectively). The expression of NAT-Rad18 and Rad18 genes increased in brain tissue of Alzheimer's control group (p = 0.002 and p = 0.04 respectively) while reduced in PBMCs of Alzheimer's control and experimental groups (p = 0.005 and p = 0.045 for NAT-Rad18, p = 0.01 and p = 0.006 for Rad18).

 ROC curve analysis showed 100% sensitivity and 85.7% specificity for the Sorl1 gene with 0.911 under the curve area and 100% sensitivity and 100% specificity for NAT-Rad18 and Rad18, separately with one under the curve area. Decreased expression in Sorl1, NAT-Rad18, and Rad18 genes can be used as blood biomarkers for diagnosis independently. However, studies on Alzheimer's patients are needed.