Astrocytes are glial cells in the brain essential for maintaining neural homeostasis, modulating synaptic activity through gliotransmission, and supporting metabolic processes. As part of Alzheimer's disease (AD) progression, astrocytes undergo significant morphological and functional changes, transitioning to reactive states that can contribute to both neuroprotection and neurodegeneration. This review aims to summarize current knowledge on the roles of astrocytes in AD, focusing on their contributions to amyloid-β (Aβ) and tau pathologies, neuroinflammation, disrupted calcium signaling, and age-related changes. We synthesized findings from published studies investigating astrocytic sodium channels (Nav1.6), key molecular pathways such as apolipoprotein E (ApoE), oxidative stress, and excitatory amino acid transporter 2 (EAAT2), as well as emerging astrocytic biomarkers including GFAP, YKL-40, and MAO-B. Optogenetic studies and other experimental approaches with high spatiotemporal resolution were also considered to understand astrocyte involvement in circuit impairments and sleep deficits in AD. Astrocytes in AD exhibit altered calcium signaling, impaired gliotransmission, and dysregulated sodium channel activity. Reactive astrocytes influence Aβ and tau pathology, contribute to neuroinflammation, and show altered biomarker expression. Molecular dysfunctions, including changes in ApoE, EAAT2, and oxidative stress pathways, exacerbate disease progression. Emerging therapeutic strategies targeting astrocytic pathways, such as siRNA therapy and gene editing, show promise for mitigating these pathological changes. Understanding the complex roles of astrocytes in AD highlights their dual protective and detrimental functions and identifies novel avenues for therapeutic intervention. Targeting astrocytic dysfunction may offer strategies to slow disease progression and improve cognitive outcomes.
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