Astrocytes in Alzheimer's disease

Abstract

Alzheimer’s disease (AD) is the most common form of dementia, characterised by progressive cognitive decline, memory loss, and impaired self-care. Main pathogenetic mechanisms include the accumulation of αamyloid plaques, neurofibrillary tangles, neuronal death, reactive gliosis, neuroinflammation, synaptic and mitochondrial malfunction, as well as disturbances in ion and neurotransmitter homeostasis. In recent years, increasing attention has been paid to the role of astrocytes in AD pathogenesis, given their capacity for metabolic support of neurons, regulation of synaptic transmission, neurovascular interaction, and homeostatic control. The review presents astrocyte subtypes and their current classifications. Age-related changes in astrocytes that may contribute to the development of cognitive impairment are also discussed. The article provides a comprehensive overview of astrocyte alterations in AD and their involvement in the pathogenesis of this neurodegenerative disorder. It summarises current understanding of the heterogeneity of astroglial changes depending on disease stage — from early reactive states to late-stage atrophy and degeneration. The review highlights the role of astrocytes in maintaining synaptic activity, glutamate and energy metabolism, glymphatic clearance, and their contribution to inflammatory processes, oxidative stress, ferroptosis, and blood–brain barrier disruption. Particular attention is given to signalling pathways mediating astrocyte reactivity and regulation of β-amyloid and tau pathology. Potential therapeutic targets aimed at supporting the homeostatic functions of astrocytes and reducing their neurotoxicity are also discussed.