Severe reactive astrocytes precipitate pathological hallmarks of Alzheimer’s disease via H2O2− production
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Star-shaped support cells of the brain known as astrocytes can, when strongly reactive, produce neurotoxic chemicals that worsen the course of Alzheimer’s disease.
The findings, from a team co-led by researchers at the Institute for Basic Science, suggest that tracking and targeting reactive astrocytes may help clinicians better diagnose and treat Alzheimer’s in its earliest stages.
By fine-tuning the degree of astrocyte reactivity in a mouse model, the researchers showed that not all reactive astrocytes are equally pathogenic. Mildly reactive astrocytes can reverse the morphological, molecular and functional changes that define their reactivity. In contrast, severely reactive astrocytes produce an enzyme that leads to the generation of hydrogen peroxide, which in turn can trigger irreversible brain damage and cognitive impairment.
Post-mortem samples from people who died of Alzheimer’s also showed signs of excess severe reactive astrocytes in the brain, as did a brain-on-a-chip, three-dimensional cell-culture model.
- Nature Neuroscience 23, 1555–1566 (2020). doi: 10.1038/s41593-020-00735-y