Researchers at the University of Vermont have discovered a way to reverse faulty blood flow in the brain linked to dementia by replacing a missing phospholipid. Their study shows that low levels of PIP2 cause overactive Piezo1 proteins in blood vessels, disrupting circulation. Restoring PIP2 normalized flow in preclinical tests, offering hope for new treatments.
A team led by Osama Harraz, Ph.D., an assistant professor of pharmacology at the University of Vermont Robert Larner, M.D. College of Medicine, has identified a key mechanism behind reduced brain blood flow in dementia. Published on December 22 in Proceedings of the National Academy of Sciences, their preclinical research focuses on the protein Piezo1, which lines blood vessel cells and senses pressure from blood movement.
The study, titled "PIP2 Corrects an Endothelial Piezo1 Channelopathy," reveals that in conditions like Alzheimer's disease, abnormally high Piezo1 activity starves brain tissue of oxygen. This stems from depleted levels of PIP2, a phospholipid in cell membranes that normally suppresses Piezo1. When PIP2 drops, the protein becomes overactive, impairing circulation. By supplementing PIP2, the researchers restored balanced blood flow, suggesting a pathway to alleviate dementia symptoms.
"This discovery is a huge step forward in our efforts to prevent dementia and neurovascular diseases," Harraz said. "We are uncovering the complex mechanisms of these devastating conditions, and now we can begin to think about how to translate this biology into therapies."
Alzheimer's and related dementias impact about 50 million people globally, with numbers rising due to aging populations. The Harraz lab's work builds on prior findings about Piezo1's role in genetic variations affecting blood flow. Future research will examine PIP2's direct interaction with Piezo1 and disease-related declines in the lipid, aiming to develop targeted therapies for vascular issues in dementia.
