The Effects of Different Exercise Protocols on the Management and Improvement of Alzheimer's Disease in Preclinical Studies: A Review Article
محورهای موضوعی : Exercise Physiology and Performance
ali jalalidehkordi
1
,
Amir Jahanbakhsh
2
,
Kamran Tavakol
3
1 - Department of Sport Physiology, Urmia University, Urmia, Iran
2 - Department of Sport Physiology, Isf.C., Islamic Azad University, Isfahan, Iran
3 - Howard University College of Medicine; Washington, DC, USA
کلید واژه: Alzheimer’s disease, Physical exercise, Aerobic training, Animal models , Cognitive function , Neurotrophic factors,
چکیده مقاله :
Numerous studies in animal models have shown that physical exercise (PE) can have positive effects on brain function and health. Alzheimer’s Disease (AD) is the most common type of dementia, characterized by the extracellular accumulation of amyloid-beta (Aβ) and neurofibrillary tangles, leading to progressive cognitive decline. This study presents a systematic review of research conducted between 2020 and 2025 regarding the effects of physical activity on animal models of AD. Sources were searched from reputable databases including PubMed, Scopus, and Google Scholar using the keywords: Alzheimer, physical exercise, animal model, and aerobic training. After applying inclusion and exclusion criteria, 23 studies were selected for final review. Aerobic exercise was the most commonly used protocol, with treadmill running being the predominant method. The most frequent training duration was 60 minutes per day at moderate intensity, five sessions per week. The animal models used mainly included Tg-APP/PS1 transgenic mice, i.c.v. Aβ injection models, and streptozotocin models. Findings indicated that PE was effective in improving cognitive markers and reducing Aβ and inflammatory proteins. The lack of studies on resistance training in AD models highlights a gap that should be addressed in future research. It is recommended that exercise protocols be tailored to the species, strain, and lifespan of the animals.
Numerous studies in animal models have shown that physical exercise (PE) can have positive effects on brain function and health. Alzheimer’s Disease (AD) is the most common type of dementia, characterized by the extracellular accumulation of amyloid-beta (Aβ) and neurofibrillary tangles, leading to progressive cognitive decline. This study presents a systematic review of research conducted between 2020 and 2025 regarding the effects of physical activity on animal models of AD. Sources were searched from reputable databases including PubMed, Scopus, and Google Scholar using the keywords: Alzheimer, physical exercise, animal model, and aerobic training. After applying inclusion and exclusion criteria, 23 studies were selected for final review. Aerobic exercise was the most commonly used protocol, with treadmill running being the predominant method. The most frequent training duration was 60 minutes per day at moderate intensity, five sessions per week. The animal models used mainly included Tg-APP/PS1 transgenic mice, i.c.v. Aβ injection models, and streptozotocin models. Findings indicated that PE was effective in improving cognitive markers and reducing Aβ and inflammatory proteins. The lack of studies on resistance training in AD models highlights a gap that should be addressed in future research. It is recommended that exercise protocols be tailored to the species, strain, and lifespan of the animals.
1. Lozupone M, Dibello V, Sardone R, Castellana F, Zupo R, Lampignano L, et al. Lessons learned from the failure of solanezumab as a prospective treatment strategy for Alzheimer’s disease. Expert Opinion on Drug Discovery. 2024;19(6):639-47.
2. Abdallat M, Abumurad SK, Tarazi A, Ammar A, Zyoud MA, AlMomani D. Deep brain stimulation and Parkinson disease: a bibliometric and visual analysis (1993–2023). Neurosurgical Review. 2025;48(1):1-15.
3. Elsworthy RJ, Dunleavy C, Whitham M, Aldred S. Exercise for the prevention of Alzheimer's disease: multiple pathways to promote non-amyloidogenic AβPP processing. Aging and Health Research. 2022;2(3):100093.
4. Mattson MP, Leak RK. The hormesis principle of neuroplasticity and neuroprotection. Cell Metabolism. 2024;36(2):315-37.
5. Hu J, Huang B, Chen K. The impact of physical exercise on neuroinflammation mechanism in Alzheimer’s disease. Frontiers in Aging Neuroscience. 2024;16:1444716.
6. Zhao R. Exercise mimetics: A novel strategy to combat neuroinflammation and Alzheimer’s disease. Journal of Neuroinflammation. 2024;21(1):40.
7. Bian R, Xiang L, Su Z. Harnessing the benefits of physical exercise-induced melatonin: A potential promising approach to combat Alzheimer’s disease by targeting beta-amyloid (Aβ). Hormones. 2024:1-11.
8. Zhang S, Gu B, Zhen K, Du L, Lv Y, Yu L. Effects of exercise on brain-derived neurotrophic factor in Alzheimer's disease models: a systematic review and meta-analysis. Archives of gerontology and geriatrics. 2024:105538.
9. Wang Q, Hu F-R, Gou X-C, Wang S, Ji N-C. Aerobic Exercise Ameliorates Alzheimer’s Disease-Like Pathology by Regulating Hepatic Phagocytosis of Aβ. Frontiers in Bioscience-Landmark. 2025;30(4):36597.
10. Molaei A, Hatami H, Dehghan G, Sadeghian R, Khajehnasiri N. Synergistic effects of quercetin and regular exercise on the recovery of spatial memory and reduction of parameters of oxidative stress in animal model of Alzheimer's disease. EXCLI journal. 2020;19:596.
11. Jaberi S, Fahnestock M. Mechanisms of the beneficial effects of exercise on brain-derived neurotrophic factor expression in Alzheimer’s disease. Biomolecules. 2023;13(11):1577.
12. Baranowski BJ, Mohammad A, Finch MS, Brown A, Dhaliwal R, Marko DM, et al. Exercise training and BDNF injections alter amyloid precursor protein (APP) processing enzymes and improve cognition. Journal of Applied Physiology. 2023;135(1):121-35.
13. Belaya I, Ivanova M, Sorvari A, Ilicic M, Loppi S, Koivisto H, et al. Astrocyte remodeling in the beneficial effects of long-term voluntary exercise in Alzheimer’s disease. Journal of neuroinflammation. 2020;17:1-19.
14. Wang M, Zhang H, Liang J, Huang J, Chen N. Exercise suppresses neuroinflammation for alleviating Alzheimer’s disease. Journal of neuroinflammation. 2023;20(1):76.
15. Ribarič S. Physical exercise, a potential non-pharmacological intervention for attenuating neuroinflammation and cognitive decline in Alzheimer’s disease patients. International journal of molecular sciences. 2022;23(6):3245.
16. Valenzuela PL, Castillo-García A, Morales JS, de la Villa P, Hampel H, Emanuele E, et al. Exercise benefits on Alzheimer’s disease: State-of-the-science. Ageing research reviews. 2020;62:101108.
17. Meng Q, Lin M-S, Tzeng I. Relationship between exercise and Alzheimer’s disease: a narrative literature review. Frontiers in neuroscience. 2020;14:507046.
18. Siddappaji KK, Gopal S. Molecular mechanisms in Alzheimer's disease and the impact of physical exercise with advancements in therapeutic approaches. AIMS neuroscience. 2021;8(3):357.
19. Pedrinolla A, Venturelli M, Fonte C, Tamburin S, Di Baldassarre A, Naro F, et al. Exercise training improves vascular function in patients with Alzheimer’s disease. European Journal of Applied Physiology. 2020;120:2233-45.
20. Yu F, Vock DM, Zhang L, Salisbury D, Nelson NW, Chow LS, et al. Cognitive effects of aerobic exercise in Alzheimer’s disease: a pilot randomized controlled trial. Journal of Alzheimer’s Disease. 2021;80(1):233-44.
21. Wei C, Wu X, Li C, Zhang Y, Yuan Q, Huang R. Aerobic exercise regulates gut microbiota profiles and metabolite in the early stage of Alzheimer's disease. The FASEB Journal. 2025;39(2):e70327.
22. Cai J, Chen Y, She Y, He X, Feng H, Sun H, et al. Aerobic exercise improves astrocyte mitochondrial quality and transfer to neurons in a mouse model of Alzheimer's disease. Brain Pathology. 2025;35(3):e13316.
23. de Andrade Santos F, Passos A, Arida RM, Teixeira-Machado L. Effectiveness of Resistance Exercise on Cognitive Function in Animal Models of Alzheimer Disease: A Systematic Review and Meta-Analysis. The Journal of Prevention of Alzheimer's Disease. 2024;11(4):998-1012.
24. Guo C, Kong X, Fan Y, Zhang R. Aerobic treadmill exercise upregulates epidermal growth factor levels and improves learning and memory in d-galactose-Induced aging in a mouse model. American Journal of Alzheimer's Disease & Other Dementias®. 2023;38:15333175231211082.
25. Bareiss SK, Johnston T, Lu Q, Tran TD. The effect of exercise on early sensorimotor performance alterations in the 3xTg-AD model of Alzheimer’s disease. Neuroscience research. 2022;178:60-8.
26. Liu Y, Chu JMT, Yan T, Zhang Y, Chen Y, Chang RCC, et al. Short-term resistance exercise inhibits neuroinflammation and attenuates neuropathological changes in 3xTg Alzheimer’s disease mice. Journal of neuroinflammation. 2020;17:1-16.
27. Paillard T, Blain H, Bernard PL. The impact of exercise on Alzheimer’s disease progression. Expert Review of Neurotherapeutics. 2024;24(4):333-42.
28. Thurlow F, Huynh M, Townshend A, McLaren SJ, James LP, Taylor JM, et al. The effects of repeated-sprint training on physical fitness and physiological adaptation in athletes: a systematic review and meta-analysis. Sports medicine. 2024;54(4):953-74.
29. Mang ZA, Ducharme JB, Mermier C, Kravitz L, de Castro Magalhaes F, Amorim F. Aerobic adaptations to resistance training: the role of time under tension. International journal of sports medicine. 2022;43(10):829-39.
30. Schenk S, Sagendorf TJ, Many GM, Lira AK, de Sousa LG, Bae D, et al. Physiological adaptations to progressive endurance exercise training in adult and aged rats: insights from the Molecular Transducers of physical activity Consortium (MoTrPAC). Function. 2024;5(4):zqae014.
31. Wu S, Jiang H. Examining the impact of differing caffeine dosages in conjunction with plyometric training on physiological adaptations in basketball players. Scientific Reports. 2024;14(1):15571.
