How Physical Activity Enhances Memory in Alzheimer's Disease

Alzheimer's disease (AD) is a progressive neurodegenerative disorder that primarily affects older individuals and is the leading cause of dementia worldwide. Characterized by a gradual decline in cognitive functions, AD results from neuronal dysfunction that accumulates over decades. As the prevalence of AD is expected to triple by 2050, identifying effective strategies to prevent or slow its progression is a major scientific priority.

Recent research has highlighted the beneficial effects of physical exercise in reducing the risk and mitigating the progression of AD. A team at Baylor College of Medicine, including Dr. Zheng Sun and Dr. Hu Chen, have investigated how exercise influences brain function using an Alzheimer's mouse model. Their study, published in Alzheimer's & Dementia, sheds light on the molecular mechanisms by which physical activity may protect cognitive health.

The research focused on how regular wheel-running exercise alters gene expression and chromatin accessibility in the hippocampus—the brain area crucial for learning and memory. Using advanced techniques like single-nucleus RNA sequencing and chromatin analysis, the team examined both healthy mice and those genetically modified to develop AD-like symptoms, including amyloid deposition.

Their findings revealed that exercise enhances learning and memory by promoting beneficial changes in gene activity. Notably, mice with AD features exhibited impaired pathways related to epidermal growth factor receptor (EGFR) and insulin signaling, which are vital for cellular health. Exercise countered these deficits by boosting EGFR and insulin activity. Blocking these pathways pharmacologically nullified the memory improvements prompted by exercise.

Further, the researchers observed increased blood levels of heparin-binding EGF (HB-EGF) —a growth factor associated with brain health—in exercised mice. Administering HB-EGF intranasally to sedentary AD mice improved their memory and reduced amyloid build-up, implicating HB-EGF as a key factor in exercise-induced cognitive benefits.

These results suggest that physical activity influences critical signaling pathways linked to brain resilience and may inform future therapeutic approaches for AD. The interplay between EGFR signaling and insulin in the brain underscores a complex connection that could also relate to the inverse relationship observed between cancer and AD.

Looking ahead, further research is needed to identify additional molecular players involved in exercise responses and to explore whether targeted delivery of growth factors like HB-EGF could serve as a preventive or therapeutic strategy for individuals at high risk of AD. While promising, these approaches require extensive testing in preclinical studies before clinical application.

In summary, engaging in regular physical activity can induce molecular changes in the brain that enhance memory and may slow the progression of Alzheimer's disease. This line of research advocates for incorporating exercise into preventive strategies against AD and opens new avenues for developing treatments based on growth factor pathways.

Source: https://medicalxpress.com/news/2025-09-qa-physical-memory-alzheimer-disease.html