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In this narrative review, we explore astrocytes\u2019 dual role in the healthy brain and the brain with AD, reflecting on the available human studies and animal models. Astrocytes are multifunctional regulators of brain homeostasis and neuronal activity within the central nervous system (CNS). These highly plastic cells undergo morphological and functional changes in response to the progression of AD, and exhibit dynamic, stage-dependent phenotypes. In the early stage of AD, astrocytes adopt a predominantly neuroprotective A2 phenotype, marked by enhanced glycolysis, A\u03b2 clearance, anti-inflammatory signaling, and synaptic support. At the intermediate stage, they shift toward an inflammatory phenotype, which consequently impairs metabolism and neurotransmitter uptake. In the late stage of AD, the A1 phenotype, characterized by inflammatory cytokine secretion, complement activation, Ca dysregulation, and mitochondrial toxicity, exacerbates AD progression. Thus, the balance between these subtypes can significantly influence the disease\u2019s trajectory, with A1 astrocytes contributing to neurotoxicity and A2 astrocytes providing neuroprotection, especially in the early stages.<\/jats:p>","DOI":"10.1177\/26331055261422166","type":"journal-article","created":{"date-parts":[[2026,2,24]],"date-time":"2026-02-24T08:33:46Z","timestamp":1771922026000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":2,"title":["Stage-Dependent Function of Astrocytes in Alzheimer\u2019s Disease: A Review"],"prefix":"10.1177","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3994-2164","authenticated-orcid":false,"given":"Helya Bolouki","family":"Azari","sequence":"first","affiliation":[{"name":"Sleep Breathing Disorders Research Center (SBDRC), Tehran University of Medical Sciences, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4870-8182","authenticated-orcid":false,"given":"Parvin","family":"Babaei","sequence":"additional","affiliation":[{"name":"Cellular &amp; Molecular Research Center, School of Medicine, Guilan University of Medical Sciences, Rasht, Iran"},{"name":"Neuroscience Research Center, Trauma Institute, School of Medicine, Guilan University of Medical Sciences, Rasht, Iran"},{"name":"Department of physiology, School of Medicine, Guilan University of Medical Sciences, Rasht, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-2665-2853","authenticated-orcid":false,"given":"Mobina","family":"Taghva Nakhjiri","sequence":"additional","affiliation":[{"name":"Breast feeding Research Center, Family Health Research Institute, Tehran University of Medical Sciences, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2026,2,24]]},"reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.2147\/NDT.S172285"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM198604103141506"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms232213954"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.neuro.24.1.1121"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-2002-4313"},{"key":"e_1_3_3_7_2","first-page":"179","volume-title":"Alzheimer Disease","author":"Terry RD","year":"1994","unstructured":"Terry RD, Masliah E, Hansen LA. 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