Background Alzheimer's disease (AD) is a progressive neurodegenerative disorder and a major cause of dementia. Objective The aim of this study was to investigate the effect of aerobic training on the expression changes of Notch1, Rbpjk, Hes1, and Hey1genes in the hippocampus of Alzheimer rats. Methods Forty, 8-week-old male Wistar rats were divided into four groups: control (n = 10), exercise (n = 10), AD (n = 10), AD + exercise (n = 10). Endurance training was implemented with increasing intensity starting at 15 m/min in the first week and progressing to speeds of 16–20 m/min over the next five weeks with increased durations each week. After 6 weeks, animals were euthanized and hippocampus was collected, frozen and RNA was isolated to quantify Notch1, Rbpjk, Hes1, and Hey1 expression. All statistical analyses and graphs were conducted using SPSS and visualized using GraphPad Prism, with significance set at p < 0.05. Results One-way analysis of variance with Tukey's post-hoc analysis found that the Alz group had significantly lower expression of Notch1 with increased expression of Rbpjk and Hes1. Conversely, the AD + Ex group was observed to have significantly higher Notch1 and significantly lower Rbpjk compared to the AD group. Conclusions These findings suggest that exercise may serve as a complementary neuroprotective intervention via manipulation of Notch1 signaling. Overall, the study highlights the need for further research on the relationship between physical activity and gene expression in the context of AD.
