Healthcare (Commonwealth Union) – Plaques have always been a key concern in Alzheimer’s disease.
Researchers at Baylor College of Medicine have identified a naturally occurring process that clears away existing amyloid plaques in the brains of Alzheimer’s mouse models and helps maintain cognitive abilities. This process works by activating astrocytes—star-shaped brain cells—to break down and remove the harmful amyloid buildup commonly seen in Alzheimer’s disease. Boosting levels of Sox9, a crucial protein that governs astrocyte activity during aging, sparked these cells into clearing the plaques. The findings, reported in Nature Neuroscience, point toward a possible astrocyte-focused treatment strategy to slow or reduce cognitive decline in neurodegenerative conditions.
The first author Dr. Dong-Joo Choi, who conducted the work while at Baylor’s Center for Cell and Gene Therapy and Department of Neurosurgery. Choi is now an assistant professor at the Center for Neuroimmunology and Glial Biology at the University of Texas Health Science Center in Houston indicated that astrocytes carry out a wide range of responsibilities vital for healthy brain activity, including supporting communication between neurons and contributing to memory formation and as the brain gets older, these cells undergo major changes, but it’s still unclear how these shifts relate to aging and neurodegenerative disorders.
In this study, the team explored molecular pathways linked to astrocyte aging and Alzheimer’s disease, honing in on Sox9 because it is a major controller of gene networks in aging astrocytes.
The senior author Dr. Benjamin Deneen, professor and Dr. Russell J. and Marian K. Blattner Chair in the Department of Neurosurgery; director of the Center for Cancer Neuroscience; member of the Dan L Duncan Comprehensive Cancer Center at Baylor; and principal investigator at the Texas Children’s Duncan Neurological Research Institute stated that they altered Sox9 expression to better understand how this protein contributes to maintaining astrocyte health in the aging brain and in Alzheimer’s disease models.
“An important point of our experimental design is that we worked with mouse models of Alzheimer’s disease that had already developed cognitive impairment, such as memory deficits, and had amyloid plaques in the brain,” explained Choi. “We believe these models are more relevant to what we see in many patients with Alzheimer’s disease symptoms than other models in which these types of experiments are conducted before the plaques form.”
The researchers either boosted or removed Sox9 in these Alzheimer’s mouse models and then monitored each animal’s cognitive performance for six months, testing how well they could identify objects or locations. Once the study concluded, they examined the mice’s brains to measure the amount of plaque buildup.
They found that lowering Sox9 levels produced the opposite outcome of increasing it. Removing Sox9 sped up plaque accumulation, made astrocytes less complex, and reduced their ability to clear amyloid deposits. Raising Sox9 levels counteracted these effects, enhancing plaque removal and boosting astrocyte activity and structural complexity.
Notably, mice with elevated Sox9 maintained their cognitive abilities, suggesting that when astrocytes are supported in clearing plaques, it helps prevent the cognitive decline associated with neurodegeneration.
Deneen indicated that they observed that raising Sox9 expression triggered astrocytes to ingest an increased number of amyloid plaques, eliminating them from the brain in a similar manner to a vacuum cleaner. He further highlighted the fact that a majority of the present treatments are focused on neurons or attempt to block the production of amyloid plaques and these findings indicate that improving astrocytes’ natural ability to clear up could be just as significant.
Choi, Deneen and their team emphasize that additional studies are required to determine how Sox9 functions in the human brain over longer periods. Still, their findings pave the way for future treatments that may leverage astrocytes to combat neurodegenerative disorders.
