Autophagy as a mechanistic link between physical exercise and Alzheimer's disease.

Abstract

Alzheimer's Disease (AD), the most prevalent cause of dementia worldwide, is a neurodegenerative disorder that currently has no cure. A growing body of evidence suggests that physical exercise is a potential non-pharmacological strategy in the treatment of AD. Recent findings highlight the involvement of autophagy in the modulatory actions of physical exercise for AD. Here, we present a narrative review of the current knowledge on how exercise impacts AD, specifically focusing on its regulation of autophagic activity in animal models of Alzheimer's disease. Evidence from rodent studies further demonstrates that exercise may influence AD-related pathology through autophagy-lysosomal regulation, lysosomal homeostasis, and mitochondrial quality control, but direct human evidence remains limited. This review uniquely positions exercise-induced autophagy regulation as a central mechanistic hub, offering a novel paradigm for developing lifestyle-based interventions for AD.