GFAP and the genetic code of astrocyte activation in Alzheimer's disease.

Abstract

Astrocytes play a crucial role in controlling homeostasis of the central nervous system (CNS), synapse, metabolism and neuroimmune communications. The growing body of evidence indicates that astrocyte dysfunction plays the leading role in the pathogenesis of Alzheimer's disease (AD). Reactive astrogliosis, characterised by cell hypertrophy, transcriptional reprogramming, and elevated glial fibrillary acidic protein (GFAP) expression, arises early in response to amyloid-β accumulation, neuroinflammation, and blood-brain barrier (BBB) disruption. Transcriptional, epigenetic and inflammatory signalling, including JAK/STAT3, NF-KB, MAPK and non-coding RNAs, control the expression of GFAP, which is a structural intermediate filament protein. High GFAP shows activation of astrocytes and a part of disrupted neuronal support, glutamate imbalance, oxidative distress and defective glymphatic clearance. Consequently, GFAP is an efficient biomarker in CSF, plasma, and saliva, which is associated with amyloid pathology, cognitive impairment, and AD. The knowledge of the astrocyte responses to GFAP can be used to extract significant information about AD mechanisms and find opportunities to identify diagnosis, prognosis and therapy.