Exercise and estrogen: common pathways in Alzheimer's disease pathology

Alzheimer's disease (AD) is a neurodegenerative disease that is characterized by progressive declines in cognitive function. Current epidemiological data indicate significant sex-linked disparities, where females have a higher risk of developing AD compared with male counterparts. This disparity necessitates further investigations to uncover the pathological and molecular factors influencing these sex differences. Although the underlying pathways behind this observed disparity remain elusive, recent research points to menopausal estrogen loss as a potential factor. Estrogen holds a significant role in amyloid precursor protein (APP) processing and overall neuronal health through the regulation of brain-derived neurotrophic factor (BDNF), a factor that is also reduced in postmenopausal women. BDNF is a known contributor to neuronal health and its reduced expression is typically linked to AD disorders. Exercise is known to increase BDNF and may provide an accessible activity for postmenopausal women to reduce their risk of AD. This review aims to discuss the relationship between estrogen, exercise, and BDNF in AD pathology.