Astrocytes and cognitive resilience in Alzheimer’s disease

Alzheimer’s disease (AD) pathology does not inevitably lead to dementia, highlighting the importance of resilience mechanisms that preserve cognitive function despite amyloid and tau accumulation. Emerging evidence implicates astrocytes as key regulators of resilience through their roles in synaptic homeostasis, neuroimmune signaling, oxidative stress responses, and neurovascular function. Recent transcriptomic, genetic, neuropathological, biomarker, and stem cell-based studies have identified resilience-associated astrocytic signatures, including interferon-related states, metallothionein-associated oxidative stress responses, and attenuated GFAP-associated responses linked to preservation of synaptic integrity. However, whether these astrocytic signatures causally contribute to resilience remains unclear. Aging-associated astrocytic alterations and comorbid pathologies further suggest that resilience reflects both protective mechanisms and differences in underlying biological vulnerability. This review summarizes current evidence linking astrocytes to cognitive resilience in AD, highlights candidate astrocytic pathways that warrant mechanistic investigation, and discusses how astrocyte-associated resilience mechanisms may inform biomarker interpretation, risk stratification, and therapeutic strategies aimed at preserving brain function despite pathology.