Astrocytes and Their Role in the Development and Progression of Alzheimer’s Disease: Gatekeepers of Neurodegeneration

Astrocytes are increasingly recognized as central players in the pathogenesis of Alzheimer's disease (AD), exhibiting both neuroprotective and neurotoxic functions, which complicates their role in disease progression. Under physiological conditions, astrocytes support neuronal homeostasis, facilitate synaptic function, and promote the clearance of Amyloid-β (Aβ), thereby contributing to neuroprotection. In the context of AD, however, reactive astrocytes can adopt detrimental phenotypes, releasing pro-inflammatory cytokines, generating oxidative stress, and disrupting neuronal networks, thereby exacerbating neurodegeneration. Consequently, the shift from a protective to a neurotoxic phenotype may not only drive neuronal loss but also accelerate AD progression. The dual roles of astrocytes and the dynamic changes in their functions-protecting neurons under normal conditions while promoting pathology when dysregulated-underscore their complex contribution to AD pathophysiology. Elucidating the mechanisms underlying astrocyte-mediated neuroprotection and neurotoxicity is essential for developing targeted therapeutic strategies aimed at modulating astrocyte activity to slow or prevent disease progression. This review aims to present and critically discuss recent advances and ongoing controversies concerning the involvement of astrocytes in AD.