Astrocyte Reactivity in Alzheimer's Disease: Therapeutic Opportunities to Promote Repair

Abstract

Astrocytes are fast climbing the ladder of importance in neurodegenerative disorders, particularly in Alzheimer's Disease (AD), with the prominent presence of reactive astrocytes surrounding amyloid-β plaques, together with activated microglia. Reactive astrogliosis, implying morphological and molecular transformations in astrocytes, seems to precede neurodegeneration, suggesting a role in the development of the disease. Single-cell transcriptomics has recently demonstrated that astrocytes from AD brains are different from "normal" healthy astrocytes, showing dysregulations in areas such as neurotransmitter recycling, including glutamate and GABA, and impaired homeostatic functions. However, recent data suggest that the ablation of astrocytes in mouse models of amyloidosis results in an increase in amyloid pathology, worsening of the inflammatory profile, and reduced synaptic density, indicating that astrocytes mediate neuroprotective effects. The idea that interventions targeting astrocytes may have great potential for AD has therefore emerged, supported by a range of drugs and stem cell transplantation studies that have successfully shown a therapeutic effect in mouse models of AD. In this article, we review the latest reports on the role and profile of astrocytes in AD brains and how manipulation of astrocytes in animal models has paved the way for the use of treatments enhancing astrocytic function as future therapeutic avenues for AD.

Keywords: Alzheimer’s disease; Astrocyte; amyloid-β; epithelial layer; glial cells; neuroprotective effects.