Researchers at Baylor College of Medicine report that raising levels of the protein Sox9 in astrocytes enables these brain support cells to remove existing amyloid plaques and preserve cognitive performance in mouse models of Alzheimer’s disease that already show memory deficits. The findings, published in Nature Neuroscience, highlight astrocytes as a potential target for slowing neurodegenerative decline.
In a study reported in Nature Neuroscience, scientists examined how astrocytes — star-shaped support cells in the brain — change with age and contribute to Alzheimer’s disease.
The team focused on Sox9, a protein that influences a wide network of genes involved in astrocyte aging and function, according to materials released by Baylor College of Medicine via ScienceDaily. Researchers manipulated Sox9 expression to assess its impact on amyloid plaque clearance and brain function in mouse models.
The experiments used Alzheimer’s mouse models that had already developed cognitive impairments, such as memory deficits, and had amyloid plaques in the brain — a design the authors argue is more relevant to symptomatic human patients than models treated before plaques form. In these animals, the researchers either increased or removed Sox9 and then monitored each mouse’s cognitive performance for six months. During this period, the mice were tested on their ability to recognize familiar objects and locations. After the behavioral testing, the team examined brain tissue to measure plaque accumulation.
The results showed a clear divergence depending on Sox9 levels. Lowering Sox9 accelerated plaque buildup, reduced the structural complexity of astrocytes and diminished their plaque-clearing capacity. Raising Sox9 had the opposite effect, increasing astrocyte activity, promoting plaque removal and preserving cognitive performance over the six-month observation period.
"We found that increasing Sox9 expression triggered astrocytes to ingest more amyloid plaques, clearing them from the brain like a vacuum cleaner," said corresponding author Dr. Benjamin Deneen, a professor in the Department of Neurosurgery at Baylor and director of the Center for Cancer Neuroscience. First author Dr. Dong-Joo Choi noted that astrocytes carry out diverse and essential functions, including supporting brain communication and memory storage, yet how age-related changes in these cells shape neurodegeneration is still not well understood.
The findings suggest that enhancing astrocytes’ natural ability to remove amyloid deposits could complement existing neuron-focused approaches to Alzheimer’s therapy. However, the investigators caution that additional research is needed to understand how Sox9 behaves in the human brain over time and to determine whether similar strategies could be translated into safe and effective treatments.
The work, led by scientists at Baylor College of Medicine and Texas Children’s Hospital, involved multiple collaborators and was supported in part by grants from the U.S. National Institutes of Health and philanthropic foundations, according to the Baylor release.
