[Astrocytes as a key structural and functional component in the development of mixed dementia]

Mixed dementia, characterized by a combination of Alzheimer's disease and cerebrovascular disease (CVD), is prevalent among the elderly population. Accumulated evidence suggests that CVD plays an active role in the neurodegenerative process, enhancing the amyloid and tau pathways and contributing to the progressive disintegration of the brain's functional and structural networks. This review presents data indicating that astrocytes serve as a critical integrative component, linking the pathologies associated with beta-amyloid and tau protein, dysfunction of the neurovascular unit, blood-brain barrier disorders, and alterations in the glymphatic system in patients with mixed dementia. We discuss the homeostatic roles of astrocytes along with their reactive transformations, characterized by enhanced Ca²⁺ signaling, metabolic interactions, polarization of aquaporin-4 (AQP4), and various inflammatory phenotypes. Astrocytes emerge as key modulators of systemic brain activity organization and as a central link uniting the pathological processes in mixed dementia. Targeting astrocyte-mediated mechanisms may pave the way for novel therapeutic approaches to address beta-amyloid and tau-proteinopathies.