The Role of Astrocytes in Synaptic Dysfunction and Memory Deficits in Alzheimer's Disease

Abstract

Astrocytes are the most abundant glial cells in the brain. They play critical roles in synapse formation and function, neurotransmitter release and uptake, the production of trophic factors, and energy supply for neuronal survival. In addition to producing proteases for amyloid-β degradation, astrocytes express various receptors, transporters, gliotransmitters, and other molecules that enable them to sense and respond to external signals. They are also implicated in amyloid-β clearance. In Alzheimer’s disease, excessive accumulation of amyloid-β induces the polarization of astrocytes into the A1 phenotype, promoting the release of inflammatory cytokines and mitochondrial reactive oxygen species, leading to alterations in astrocytic functions. Under such conditions, gliotransmitter release, glutamate neurotransmission, AMPA receptor trafficking, and both Hebbian and non-Hebbian forms of synaptic plasticity—biological activities essential for synaptic functions—are compromised. Moreover, astrocytes are essential for learning, memory, and synaptic plasticity, and alterations in their function are associated with memory deficits in Alzheimer’s disease. This review provides an overview of the current understanding of the defects in astrocytes that lead to altered synaptic functions, neuronal structural plasticity, and memory deficits in Alzheimer’s disease.