Researchers at Baylor College of Medicine have discovered a process that can eliminate amyloid plaques from the brains of mice with Alzheimer’s disease, while also helping to maintain memory and cognitive function. This finding focuses on astrocytes, star-shaped support cells in the brain, which can be instructed to remove the toxic plaque deposits typically associated with Alzheimer’s.
The study revealed that increasing levels of Sox9, a protein essential for regulating astrocyte function as the brain ages, significantly enhanced the cells’ ability to clear amyloid plaques. The research, published in Nature Neuroscience, suggests a possible approach to treatment that boosts the brain’s support system to slow down cognitive decline linked to neurodegenerative conditions.
Astrocytes and Brain Function
“Astrocytes are involved in various essential tasks for normal brain functionality, like aiding communication and memory storage. However, as the brain ages, astrocytes undergo significant changes, and the implications of these shifts in the context of aging and neurodegeneration remain largely unclear,” noted Dr. Dong-Joo Choi, the first author of the study, who conducted the research at Baylor’s Center for Cell and Gene Therapy and Department of Neurosurgery. Choi is now an assistant professor at the University of Texas Health Science Center at Houston.
Sox9 and Aging Astrocytes
In this investigation, researchers aimed to gain insights into how astrocytes change with age and how these changes relate to Alzheimer’s disease, focusing specifically on Sox9 because it regulates numerous genes in aging astrocytes.
“We altered the expression of the Sox9 gene to evaluate its role in sustaining astrocyte function in both aging brains and Alzheimer’s disease models,” explained Dr. Benjamin Deneen, the corresponding author and a professor at the Department of Neurosurgery, as well as the director of the Center for Cancer Neuroscience at Baylor.
Testing in Mice With Established Symptoms
“A key aspect of our experimental design was working with mouse models of Alzheimer’s disease that already showed cognitive impairments, like memory issues, coupled with amyloid plaques in the brain,” Choi remarked. “We believe these models better represent the symptoms found in many Alzheimer’s patients compared to models where experiments are done before plaque formation occurs.”
The researchers increased or decreased Sox9 in these mice and monitored their cognitive performance over six months, evaluating their ability to recognize familiar objects and environments. At the study’s conclusion, they assessed the plaque accumulation in the brain.
Boosting Sox9 Improves Plaque Clearance and Memory
The results highlighted a distinct difference. Lower levels of Sox9 were linked to accelerated plaque buildup, simpler astrocyte structures, and a decreased capacity to clear amyloid deposits. Conversely, raising Sox9 levels had the opposite effect, improving astrocyte activity, increasing their structural complexity, and encouraging plaque removal.
Significantly, mice with elevated Sox9 levels exhibited better cognitive functions, indicating that activating astrocytes to clear plaques may help slow the mental decline related to Alzheimer’s disease.
“We discovered that boosting Sox9 expression prompted astrocytes to absorb more amyloid plaques, clearing them from the brain like a vacuum cleaner,” Deneen remarked. “While most current treatments concentrate on neurons or aim to prevent amyloid plaque formation, this study implies that enhancing astrocytes’ inherent cleanup abilities might be equally crucial.”
A New Direction for Alzheimer’s Treatment
The researchers stress the necessity for further investigation into the role of Sox9 in the human brain over time. Nonetheless, the findings pave the way for novel therapies that leverage astrocytes as a natural defense against neurodegenerative diseases.
Research Team and Funding
Other contributors to the study from Baylor College of Medicine include 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.
This research received support from several National Institutes of Health grants. Additional funding was as well provided by various foundations and resources from Houston Methodist and Baylor College of Medicine.
