Role of astrocytes in Alzheimer's disease pathogenesis and the impact of exercise-induced remodeling

Abstract

Alzheimer's disease (AD) is a prevalent and debilitating brain disorder that worsens progressively with age, characterized by cognitive decline and memory impairment. The accumulation of amyloid-beta (Aβ) leading to amyloid plaques and hyperphosphorylation of Tau, resulting in intracellular neurofibrillary tangles (NFTs), are primary pathological features of AD. Despite significant research investment and effort, therapies targeting Aβ and NFTs have proven limited in efficacy for treating or slowing AD progression. Consequently, there is a growing interest in non-invasive therapeutic strategies for AD prevention. Exercise, a low-cost and non-invasive intervention, has demonstrated promising neuroprotective potential in AD prevention. Astrocytes, among the most abundant glial cells in the brain, play essential roles in various physiological processes and are implicated in AD initiation and progression. Exercise delays pathological progression and mitigates cognitive dysfunction in AD by modulating astrocyte morphological and phenotypic changes and fostering crosstalk with other glial cells. This review aims to consolidate the current understanding of how exercise influences astrocyte dynamics in AD, with a focus on elucidating the molecular and cellular mechanisms underlying astrocyte remodeling. The review begins with an overview of the neuropathological changes observed in AD, followed by an examination of astrocyte dysfunction as a feature of the disease. Lastly, the review explores the potential therapeutic implications of exercise-induced astrocyte remodeling in the context of AD.