Revitalizing Aging Brain Cells in Mice by Boosting a Single Protein, Study Reveals

Scientists at Baylor College of Medicine in the United States have uncovered a mechanism that could lead to treatments targeting the protein buildups central to Alzheimer's disease. In experiments with mice engineered to mimic the condition, the team discovered that increasing levels of a protein called Sox9 stimulated specialized brain cells to aggressively remove plaques, effectively enhancing the brains natural clean-up processes.

Behavioral and memory assessments revealed that mice receiving the Sox9 intervention performed significantly better, indicating that this approach may help protect the brain and reverse cognitive decline typically seen as neurons are damaged in Alzheimer's disease.

The beneficial effects of Sox9 appear to be linked to the heightened activity of a receptor known as MEGF10, found exclusively in astrocytesbrain maintenance cells responsible for clearing amyloid-beta plaques. According to neuroscientist Dong-Joo Choi, formerly of Baylor College of Medicine and now at the University of Texas Health Science Center at Houston, Astrocytes carry out essential functions for normal brain activity, including supporting communication between neurons and memory storage. As the brain ages, their functionality changes significantly, though the implications of these changes are not fully understood.

Boosting Sox9 levels in the aging astrocytes appeared to rejuvenate these cells, improving their plaque-removal efficiency. Interestingly, elevated Sox9 has been observed in Alzheimers-affected brains before, suggesting a natural response by the brain to enhance waste clearance.

The team also conducted experiments removing Sox9 in genetically modified mice. These animals showed deteriorating astrocyte health, worsening memory performance, and an increase in amyloid-beta accumulation, reinforcing the critical role of Sox9 in maintaining brain function.

Our experiments focused on mouse models that had already developed memory deficits and amyloid plaques, Choi explains. This makes them more comparable to human patients with symptomatic Alzheimers than models tested before plaque formation.

Alzheimer's research continues from multiple angles, including approaches aimed at reducing amyloid-beta plaques, but treatment effectiveness remains varied, highlighting the complexity of the disease. While it is still unclear whether these protein clumps are a cause or consequence of Alzheimer's, each discovery brings scientists closer to understanding and potentially halting disease progression.

Although these findings are currently limited to mice, they offer a promising new strategy: enhancing astrocytes natural clean-up capabilities may be as important as targeting neurons or preventing plaque formation. As neuroscientist Benjamin Deneen notes, This study indicates that empowering the brains maintenance cells could be a vital component of future Alzheimers therapies.

The research has been published in Nature Neuroscience.

Author: Sophia Brooks