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Background and Purpose: The effect of physical activity and living in enriched environment on some cognitive mechanisms in Alzheimer's disease (AD) is not yet well understood. Therefore, this study aimed to investigate the effect of aerobic training along with enriched environment on spatial memory and brainderived neurotrophic factor in the Hippocampal tissue of elderly female Wistar rats with Alzheimer's disease. Materials and Methods: In this experimental study, 30 elderly female Wistar rats with twenty-one-monthold and average weight of 260±20 grams were used and divided into 6 groups: control-healthy, Alzheimer's, sham group, Alzheimer's + aerobic exercise (treadmill), Alzheimer's + enriched environment, Alzheimer's + enriched environment + aerobic exercise (treadmill). Rats in the training groups performed two 15-min sessions with 5-minute passive rest at a speed of 10 m/min in the first and second weeks. In the third week, they performed three sessions at a speed of 15 m/min with a 5-min break, and in the fourth week, four sessions per day at a speed of 15 m/min with a 5-min break. In the enriched environment group, the animals were kept in a plexiglass material larger than the standard cage (60 x 50 x 70 cm³). In these cages, devices such as ladders, hollow pipes, wooden blocks and plastic toys were placed. In Alzheimer's groups, rats were anesthetized by intraperitoneal injection of ketamine (80 mg/kg) and xylazine (20 mg/kg). Then, Alzheimer's Aβ was induced by intracerebroventricular injections (10μg/rat). Spatial memory was measured by Morris water maze, barin derived neurotrophic factor (BDNF) and Trk-B by western blot. In a pilot study in order to evaluate the spatial memory of rats, one week after beta-amyloid injection, all rats were divided into Alzheimer's and control groups. Rats were trained in the maze for four days and the mean percentage permanence in the platform area was recorded. The results of the independent t-test showed that there is a significant difference between the control group and Alzheimer's group (P=0.0152). Therefore, One-way analysis of variance with Tukey's post-hoc test (P<0.05) were used to analyze the data. Results: BDNF increased in all groups significantly (P<0.001), and comparisons between groups were significant except for control vs sham (P=0.27) and Alzheimer's vs Aerobic Alzheimer's (P=0.20) groups. Trk-B increased in all groups and between-group comparisons were significant except for control vs sham (P=0.22), aerobic Alzheimer's vs Alzheimer's enriched environment (P=0.32). However, for spatial memory only between-group comparisons for Alzheimer's vs control (P=0.02), and Alzheimer's vs Alzheimer's + enriched environment + aerobic training (P<0.001) groups were significant. Conclusion: Based on the findings, it can be concluded that aerobic exercise and living in enriched environment can be effective on the spatial memory of elderly Alzheimer's rats through the increase of neurotrophic factors [ABSTRACT FROM AUTHOR]