The Role of Astrocytes in the Relationship Between Tau Pathology & Synaptic Dysfunction in Alzheimer’s Disease
Abstract – Alzheimer’s disease is a progressive, neurodegenerative disorder that is the leading cause of dementia worldwide. Alzheimer’s disease is characterized by the accumulation of extracellular Amyloid-ß plaques, aggregation of the highly-phosphorylated protein tau that leads to the formation of intracellular neurofibrillary tangles, and the dysfunction of neuronal synapses. All of these molecular characteristics contribute to the severe cognitive impairment and decline seen in Alzheimer’s. Astrocytes are the most abundant type of glial cell in the central nervous system and greatly outnumber neurons. They are important in maintaining neuronal homeostasis through their various functions in synaptic regulation and transmission, astrocytic gliotransmission, and extracellular ion balance. The main objective of this review is to further investigate the role of astrocytes in Alzheimer’s disease, specifically in the relationship between tau pathology and synaptic dysfunction. After reviewing the literature, it can be concluded that the astrocytic release of various gliotransmitters, proinflammatory cytokines, and genes results in an increase of hyperphosphorylated tau and tau accumulation, thus leading to synaptic dysfunction in AD. As there has been no cure or highly efficient treatment for Alzheimer’s disease thus far, further research into the role of astrocytes in the relationship between tau pathology and synaptic dysfunction in the disease could provide alternative pathways and targets for therapeutic treatment.