Frontiers in Aging Neuroscience · Oct 19, 2026
Physical exercise: a multi-target strategy for the prevention and treatment of Alzheimer’s disease
By Tong W
Alzheimer’s disease (AD) is a devastating age-related neurodegenerative disease characterized by irreversible cognitive dysfunction and neuronal loss. The complex pathogenesis of AD involves core proteinopathies of amyloid- β (Aβ) and tau, chronic neuroinflammation, and extensive cerebral metabolic disorders, which collectively drive progressive neuronal damage and disease deterioration. Currently, effective disease-modifying drugs for AD are still lacking, and physical exercise has been recognized as a safe and effective non-pharmacological intervention to prevent and alleviate AD pathological progression. Specifically, exercise inhibits abnormal Aβ deposition and tau hyperphosphorylation, suppresses microglial overactivation and sustained neuroinflammatory responses, and remodels cerebral metabolic homeostasis by improving glucose utilization, balancing lactate metabolism, restoring mitochondrial function, and correcting dysregulated lipid metabolism. Additionally, exercise-mediated upregulation of brain-derived neurotrophic factor (BDNF) enhances neuronal survival and synaptic plasticity to block AD pathological progression. This review innovatively combines core AD pathological markers and multi-dimensional metabolic mechanisms, providing a theoretical reference for further exploring the molecular mechanism of exercise intervention in AD.