Title:Astrocyte Reactivity in Alzheimer’s Disease: Therapeutic Opportunities to
Promote Repair
Volume: 19
Issue: 1
Author(s): Nazanin Mirzaei, Nicola Davis, Tsz Wing Chau and Magdalena Sastre*
Affiliation:
- Department of Brain Sciences, Imperial College London, Hammersmith
Hospital, Du Cane Road, London W12 0NN, UK
Keywords:
Astrocyte, glial cells, Alzheimer’s disease, amyloid-β, neuroprotective effects, epithelial layer.
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.
