A brand new examine from researchers highlights an surprising participant in Alzheimer’s illness: growing older astrocytes.
Senescent astrocytes have been recognized as a significant contributor to Alzheimer’s development. The cells lose protecting capabilities and gas irritation, notably in APOE4 carriers. The findings spotlight senolytic medication as a possible new remedy.
For the primary time, the analysis crew has proven that senescent astrocytes are current within the brains of individuals with Alzheimer’s illness. These cells stay alive however have misplaced their regular perform, and their accumulation means that mobile growing older performs a direct and important function in neurodegeneration.
The findings had been printed within the Journal of Neuroinflammation. The examine was led by Dr. Antonia Gutiérrez, Professor of Cell Biology and Principal Investigator of the NeuroAD group, alongside Dr. Juan Antonio García León, Affiliate Professor of Cell Biology. The analysis crew additionally included Laura Cáceres, Laura Trujillo, Elba López, Elisabeth Sánchez, and Inés Moreno.
Astrocytes are the most typical sort of glial cell within the mind. They’re important for sustaining wholesome neurons and supporting correct mind perform. Nonetheless, the researchers discovered that in people with the strongest genetic threat issue for Alzheimer’s illness (APOE4), astrocytes present indicators of irregular early growing older.
APOE4 Genotype Drives Untimely Astrocyte Getting older
“We’ve got confirmed that these broken astrocytes not solely lose their capability to guard neurons but in addition undertake a pro-inflammatory profile that severely compromises neuronal survival,” the authors clarify. Upon coming into a state of senescence, the cells accumulate DNA injury, exhibit mitochondrial alterations—the mobile ‘powerhouses’—and ‘launch poisonous molecules that amplify irritation and tissue injury within the mind.
To analyze these processes, the scientists used induced pluripotent stem cells (iPSCs). By taking small pores and skin samples from sufferers, they had been capable of reprogram the cells within the laboratory and generate useful human astrocytes for detailed examine.
This strategy allowed the crew to look at illness mechanisms immediately in human cells, avoiding a number of the limitations of animal fashions, which don’t all the time seize the complete complexity of the human mind.
Human Validation Confirms Central Position in Neurodegeneration
The laboratory findings had been bolstered by inspecting mind tissue obtained after dying from people with Alzheimer’s illness. The evaluation strongly steered that just about 80 p.c of the cells within the cerebral cortex that displayed indicators of untimely growing older had been astrocytes. This proportion was a lot greater than what’s seen in wholesome folks of the identical age.
Collectively, these outcomes help the concept that astrocyte senescence is just not merely a byproduct of the illness however a driving power behind its development.
The invention is particularly vital given that there’s at present no efficient remedy able to curing Alzheimer’s illness or stopping its advance. In Spain alone, greater than 1.2 million persons are affected.
The findings recommend a brand new therapeutic route centered on growing modern methods similar to senolytic medication. These remedies would goal to remove or “reprogram” aged astrocytes, with the aim of preserving neurons and slowing cognitive decline.
Reference: “Human iPSC-derived APOE4/4 Alzheimer´s illness astrocytes exhibit a senescent and pro-inflammatory state that compromises neuronal help” by Laura Caceres-Palomo, Elisabeth Sanchez-Mejias, Laura Trujillo-Estrada, Juan Jose Perez-Moreno, Elba Lopez-Oliva, Tau En Lim, Leah DeFlitch, Serena H. Chang, Lucas Kampman, M. Ryan Corces, Mathew Blurton-Jones, Ines Moreno-Gonzalez, Alberto Pascual, Javier Vitorica, Juan Antonio Garcia-Leon and Antonia Gutierrez, 12 December 2025, Journal of Neuroinflammation.
DOI: 10.1186/s12974-025-03607-z
