A team of researchers at Baylor College of Medicine has identified a natural mechanism that could help preserve cognitive function in individuals suffering from Alzheimer’s disease. They discovered that by enhancing the activity of a protein known as Sox9, brain cells called astrocytes can effectively clear amyloid plaques, which are linked to cognitive decline in this neurodegenerative condition.
The study, published in the journal Nature Neuroscience, highlights the potential for astrocyte-based therapies that could alleviate symptoms associated with Alzheimer’s. By increasing Sox9 production, the researchers found that astrocytes became more efficient at removing the harmful plaques that accumulate in the brains of affected individuals.
Dr. Dong-Joo Choi, the first author of the study and an assistant professor at the University of Texas Health Science Center, noted that astrocytes have essential roles in maintaining normal brain function, including communication between brain cells and memory storage. “As the brain ages, astrocytes undergo significant functional changes; however, the role of these changes in aging and neurodegeneration remains poorly understood,” he explained.
The research team focused on understanding the mechanisms associated with astrocyte aging and the development of Alzheimer’s disease, particularly through the lens of Sox9. Dr. Benjamin Deneen, the corresponding author and a professor at Baylor College, emphasized the importance of their experimental design, which utilized mouse models of Alzheimer’s that already exhibited cognitive impairments and amyloid plaque buildup.
Over a six-month period, they manipulated the expression of Sox9 in these mice to observe its effects on cognitive function. The results were striking: increasing Sox9 expression led to enhanced clearance of amyloid plaques and a preservation of cognitive abilities, while reducing Sox9 resulted in accelerated plaque formation and diminished astrocyte functionality.
“We found that increasing Sox9 expression triggered astrocytes to ingest more amyloid plaques, acting like a vacuum cleaner for the brain,” Deneen said. This discovery contrasts with many current treatments that primarily target neurons or aim to prevent plaque formation, suggesting that boosting the natural cleanup abilities of astrocytes could be an equally vital strategy.
While the findings are promising, Choi and Deneen caution that further research is essential to understand the implications of Sox9 in the human brain over time. Nonetheless, this study paves the way for potential therapies that leverage astrocyte functions in combating neurodegenerative diseases.
The research team also included contributions from Sanjana Murali, Wookbong Kwon, Junsung Woo, Eun-Ah Christine Song, Yeunjung Ko, Debo Sardar, Brittney Lozzi, Yi-Ting Cheng, Michael R. Williamson, Teng-Wei Huang, Kaitlyn Sanchez, and Joanna Jankowsky, all affiliated with Baylor College of Medicine.
Funding for this significant research was provided by several grants from the National Institutes of Health (R35-NS132230, R01-AG071687, R01-CA284455, K01-AG083128, R56-MH133822) as well as support from the David and Eula Wintermann Foundation, the Eunice Kennedy Shriver National Institute of Child Health & Human Development, and collaborative resources from Houston Methodist and Baylor College of Medicine.
