Exploring Exercise-induced BDNF Pathways that affect Tau Dephosphorylation and Episodic Memory in Alzheimer’s Disease: A Systematic Review

Abstract

Introduction: Research has indicated that exercise improves memory and cognitive function, which can be attributed to an increase in exercise-induced brain-derived neurotrophic factor (BDNF). BDNF has also been suggested to reverse tau aggregation seen in Alzheimer’s disease (AD) via tau dephosphorylation, which can thereby improve memory function. A tyrosine receptor (TrkB) mechanism has been proposed between BDNF and the subsequent tau dephosphorylation. However, the effects of exercise-induced BDNF on tau dephosphorylation and episodic memory remain unclear. Thus, the purpose of the systemic review is to clarify a pathway linking exercise, BDNF, tau dephosphorylation, and episodic memory in AD models.

Methods: A comprehensive literature search of peer-reviewed primary and review articles was conducted in the field of neuroscience and memory. Key search terms used in the database were: BDNF, tau, phosphorylation, TrkB, exercise, memory, and Alzheimer’s disease.

Results: Evidence suggests that exercise-induced BDNF enhances episodic memory in animal and human studies, and has therapeutic potential for alleviating AD symptoms. Furthermore, bath incubation of BDNF administered to AD-induced human and rodent tissue has demonstrated a rapid tau dephosphorylation effect, specifically through a protein kinase pathway involving PI-3K and AKT, following TrkB binding.

Discussion: The memory enhancements demonstrated from increased BDNF production are dependent on exercise. Exercise-induced episodic memory enhancements may be explained by BDNF’s ability to dephosphorylate tau via a TrkB mechanism. Specifically, the PI-3K/AKT pathway is the subsequent downstream signal involved in tau dephosphorylation, since BDNF administration to AD-induced neurons resulted in no dephosphorylation in the presence of a PI-3K inhibitor. Lastly, given BDNF’s ability to dephosphorylate tau in AD models and shift tau accumulation away from the soma, it indicates that exercise may form part of an effective treatment for individuals with AD.

Conclusion: Although the research surrounding BDNF and tau dephosphorylation on episodic memory enhancements is extensive, gaps remain about BDNF’s effects in an exercise-induced setting. Further research needs to be conducted to confirm whether exercise-induced BDNF indicates similar effects on episodic memory. This research is also clinically relevant in AD treatment, whereby exercise has the potential to be prescribed concurrently with other therapies.