Researchers from the NeuroAD group at the University of Málaga have identified senescent astrocytes as a significant factor in the progression of Alzheimer's disease. The study, published in the Journal of Neuroinflammation, marks the first time that these aging cells have been observed in the brains of Alzheimer's patients.
Astrocytes are glial cells responsible for supporting and protecting neurons. According to Dr. Antonia Gutiérrez, Professor of Cell Biology and Principal Investigator of the NeuroAD group, and Dr. Juan Antonio García León, Associate Professor of Cell Biology, their research found that astrocytes in patients with the APOE4 genotype—considered to carry the highest genetic risk for Alzheimer's—show signs of premature pathological aging.
"We have confirmed that these damaged astrocytes not only lose their ability to protect neurons, but also adopt a pro-inflammatory profile that severely compromises neuronal survival," the authors state. They explain that once these cells enter senescence, they accumulate DNA damage, show mitochondrial alterations, and release toxic molecules which increase inflammation and tissue damage in the brain.
The team used induced pluripotent stem cell (iPSC) technology to reprogram skin samples from patients into functional human astrocytes for laboratory study. This approach allowed them to investigate disease mechanisms directly in human cells rather than relying solely on animal models.
The findings were further validated by analyzing postmortem brain tissue from Alzheimer's patients. Nearly 80% of cells with signs of premature aging in these samples were identified as astrocytes—a much higher proportion compared to healthy individuals.
These results suggest that astrocyte senescence plays a central role in Alzheimer's progression rather than being a secondary effect. The researchers note this is especially important given there are currently no effective treatments to cure or stop Alzheimer’s disease.
The study suggests new directions for therapeutic strategies such as developing drugs aimed at eliminating or reprogramming aged astrocytes to help protect neurons and slow cognitive decline.
This research is part of Laura Cáceres Palomo's doctoral thesis and involved collaboration with institutions including University of California Irvine, University of California San Francisco, University of Seville, Institute of Biomedicine of Seville (IBIS), and CIBERNED.
