Effect of exercise on hepatic amyloid β levels and serum LRP1 levels in animal models of Alzheimer's disease: The role of complex activity

Document Type : Research Paper

Authors
Mohsen Salamat Tometri 1
Talebi Vahid 2
Mohammad Nasri 3
1 Department of Sport Sciences, Faculty of Educational Sciences and Psychology, Shahid Madani University of Azerbaijan, Tabriz, Iran
2 Department of Sports Sciences, Faculty of Humanities, University of Maragheh, Maragheh, Iran
3 Department of Exercise Physiology, Faculty of Sport Sciences, University of Mazandaran, Babolsar, Iran
10.22089/spj.2025.18408.2393
Abstract
Extended Abstract
Background and Purpose
Alzheimer's disease is the most common cause of incurable dementia in the elderly, accounting for approximately 60–80% of cases. Impaired clearance of amyloid beta (Aβ) and its accumulation in the brain and other tissues, such as the liver, may be a key factor in the pathophysiology of Alzheimer's disease. There are several pathways for Aβ to exit the brain into the environment, among which the transport across the blood–brain barrier via low-density LRP1 is of particular importance. Previous studies have shown that physical activity, especially complex motor exercises, has significant positive effects on cognitive function and reduces the risk of Alzheimer's disease. This study was designed to enhance cognitive function by increasing motor and environmental challenges and to investigate the effect of exercise on hepatic amyloid-beta levels and serum LRP1 levels in animal models of Alzheimer's disease, considering the role : The role of cognitive motor activity.
Materials and Methods
In this experimental study, 40 male Wistar rats (4–6 weeks old) were randomly divided into 4 groups after adaptation to standard conditions (temperature 24°C, humidity 55%, light cycle 12:12 h). 1- healthy control (no intervention), 2- Alzheimer's disease control (disease induction without exercise), 3- healthy complex exercise (exercise without disease), and 4- Alzheimer's disease complex exercise (disease + exercise). The Alzheimer's disease model was induced by intraventricular injection of streptozotocin (STZ; 3 mg/kg in 5 μl distilled water) under anesthesia (ketamine 60 mg/kg + xylazine 8 mg/kg) and its validity was confirmed by the transport box test (significant reduction in time spent in the dark room; p ≤ 0.001). The exercise groups had unlimited access to a complex running wheel equipped with 22 irregular bars (changing the arrangement every 2 weeks to prevent adaptation) for 8 weeks, and daily distance was recorded with a pedometer (mean: 324-400 m/day). After the end of the period, the animals were deeply anesthetized (ketamine 50 mg/kg + xylazine 5 mg/kg) and blood serum (from the heart) and liver tissue samples were collected. The levels of hepatic beta amyloid (Aβ40) and soluble LRP1 protein (sLRP1) in serum were measured using proprietary ELISA kits from Zelbio and Antibodies Co, respectively. Data were analyzed using SPSS version 24 software and Shapiro-Wilk tests (normality test), Levine (homogeneity of variance), one-way ANOVA with Tukey's post hoc test (comparison of group means) and ANCOVA (weight changes with control for pre-test effect) (significance level p ≤ 0.05).
Results
The findings of this study showed that the time spent in the dark compartment of the shuttle box test was significantly lower in the Alzheimer's group compared to the healthy group (p=0.001), which confirms the validity of disease induction in the patient groups in the study. The results of this study also showed that the level of amyloid beta in the complex exercise group (Wheel-C) was significantly reduced compared to the healthy control and Alzheimer's control groups. These results showed a significant difference between the groups in a one-way analysis of variance to compare the level of amyloid beta among the study groups (F=33.089, p=0.001). Tukey's post hoc analysis also showed that the level of amyloid beta in the Wheel-Control group was significantly different from the control, Alzheimer's, and Wheel-Alzheimer's groups (p=0.001). The Wheel-Alzheimer group also showed a significant difference compared to the Alzheimer's group. However, this difference was not significant compared to the healthy control group. Overall, this study showed that running on a rotating wheel with irregular patterns significantly reduced amyloid beta levels in the brain and liver in an animal model of Alzheimer's disease. Analysis of sLRP levels using one-way ANOVA also showed a significant difference between groups (F = 17.103, p = 0.001). Tukey's post hoc analysis also showed that sLRP levels in the Alzheimer's group were significantly different from those in the healthy control, wheel control, and Alzheimer's wheel groups (p = 0.001) and that there was also a significant difference between the wheel control and Alzheimer's wheel groups (p = 0.041). The results of the paired t-test showed a significant increase in the subjects' weight in the post-test compared to the pre-test (p=0.001), and the results of ANCOVA also showed a significant difference in weight between the research groups.
Conclusion
The results of this study showed that the effects of exercise training are likely directly related to the activation of neurotrophic pathways, increased synaptic plasticity, improved mitochondrial function, and enhanced Aβ clearance mechanisms, particularly through the LRP1 receptor pathway in the liver and blood-brain barrier. Therefore, running on a rotating wheel with irregular patterns, by simultaneously engaging cognitive and motor systems, acts as an effective intervention that affects the brain-liver axis in the pathophysiology of Alzheimer's disease and slows the progression of the disease. Among the limitations of this study are the use of an animal model (rats) and a specific type of exercise (running on a complex wheel), which may limit the generalizability of the findings to humans. In addition, only a limited number of pathways related to Aβ clearance and cognitive function were investigated. It is recommended that future studies investigate the long-term effects of complex exercise, gender differences, more detailed assessment of Aβ-degrading enzymes, other neurobiological pathways such as tau protein phosphorylation or changes in neurogenesis, and the use of human or cellular models to increase the external validity of the results.
Key Words: Amyloid Beta, Liver, Physical Activity, LRP1, Alzheimer’s Disease
Article Message
Cognitive motor activity (such as running on a rotating wheel with an irregular bar pattern) by simultaneously stimulating both motor and cognitive systems significantly reduces Aβ levels in the brain and liver of animal models of Alzheimer's disease and increases serum levels of the Aβ clearance protein (sLRP1). These changes facilitate peripheral and central clearance of Aβ by enhancing neurotrophic pathways, improving mitochondrial function, and activating the LRP1 receptor in the liver and blood-brain barrier. The results suggest that complex exercise has therapeutic potential to slow the pathological process of Alzheimer's disease by modulating brain-liver interactions.
Ethical Considerations
All animal protocols were conducted in accordance with ethical principles, with minimal animal suffering.
Authors’ Contributions
Conceptualization: (V.T, M.S)
Data Collection: (V.T, M.N)
Data Analysis: (V.T, M.N)
Manuscript Writing: (M.S, V.T, M.N)
Review and Editing: (V.T, M.N)
Responsible for funding: (V.T, M.S)
Literature Review: (V.T, M.S)
Project Manager: (V.T)
Conflict of Interest
The authors of this study have no conflicts of interest.
Acknowledgments
We are grateful to all those who paved the way for this research.
 
Keywords
Amyloid Beta, Liver, Physical Activity, LRP1, Alzheimer&rsquo
s Disease

Main Subjects

 
 
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Sport Physiology
Volume 17, Issue 66
June 2025
Pages 86-70

  • Receive Date 22 August 2025
  • Revise Date 10 October 2025
  • Accept Date 11 October 2025