"Enhancing the natural phagocytic capability of astrocytes may represent a treatment strategy for Alzheimer's disease."
Researchers at Baylor College of Medicine have published findings demonstrating that increasing the expression of the protein Sox9 in astrocytes enables these brain cells to remove amyloid plaques and maintain cognitive function in mouse models of Alzheimer's disease. The study was published in Nature Neuroscience on November 21, 2025 (DOI: 10.1038/s41593-025-02115-w).
Study Details and Methodology
The research team manipulated Sox9 expression in astrocytes within Alzheimer's mouse models. These mice already exhibited cognitive impairment and amyloid plaques at the start of the experiment, a condition the authors described as more representative of the clinical presentation of Alzheimer's disease in humans.
- Increasing Sox9 expression in the mice resulted in enhanced structural complexity of astrocytes, increased ingestion of amyloid plaques via the MEGF10 receptor, and a reduction in amyloid buildup.
- Decreasing Sox9 expression in the mice led to faster plaque accumulation and a simpler astrocyte structure.
Behavioral Outcomes
Over a six-month period, mice with elevated Sox9 levels performed better on memory and recognition tests compared to control groups. Mice with reduced Sox9 levels experienced accelerated cognitive decline.
Background and Context
Alzheimer's disease is characterized by the accumulation of amyloid plaques in the brain and progressive cognitive decline. Astrocytes are star-shaped glial cells that support neuronal function, including communication and memory storage. As organisms age, astrocytes undergo functional changes, though their specific role in neurodegeneration has been an area of research. Sox9 is a transcription factor known to regulate multiple genes in aging astrocytes.
Funding
The research was supported by multiple sources, including National Institutes of Health grants (R35-NS132230, R01-AG071687, R01-CA284455, K01-AG083128, R56-MH133822), the David and Eula Wintermann Foundation, the Eunice Kennedy Shriver National Institute of Child Health & Human Development, and other institutional resources.
Implications and Further Research
The study suggests that enhancing the natural phagocytic capability of astrocytes may represent a treatment strategy for Alzheimer's disease. The authors noted that further research is required to understand Sox9 function in the human brain over time.