Dynamic contributions of astrocytes in Alzheimer's disease.

Abstract

In Alzheimer's disease, pathological stimuli reshape astrocyte functions, which in turn act on neurons, making astrocytes critical modulators of disease progression. A comprehensive understanding of how astrocytes dynamically shift from physiology to pathology across multiple functional domains remains to be established. This review synthesizes recent findings across four key domains: proteostasis, gliotransmission/synapse regulation, blood-brain barrier integrity and metabolism, and microglial crosstalk. For each domain, we compare homeostatic and pathological functions, analyze how supportive roles turn detrimental, and discuss effects on neuronal fate. We also examine signaling pathways that govern astrocyte reactivity and the potential of astrocyte-derived biomarkers. By tracing these dynamic transitions, we aim to refine Alzheimer's disease mechanisms and identify state-targeted therapeutic opportunities.