Scientists Find Brain Repair Target for Vascular Dementia

UCLA researchers have identified a critical mechanism that drives brain damage in vascular dementia and demonstrated that targeting it with a repurposed drug can promote brain repair and restore memory in mice.

The study, published in Cell, reveals how inflammation between blood vessels and brain cells creates a toxic cycle that expands dementia damage—and how interrupting this process could lead to the first effective treatment for this understudied disease.

Vascular dementia affects millions worldwide as the second leading cause of dementia, often occurring alongside Alzheimer’s disease in what doctors call “mixed dementia.” Unlike Alzheimer’s, no drugs exist to slow its progression or promote recovery from the brain damage it causes.

“We reasoned that the cell in the brain areas in which the disease expands will lose their normal signaling with each other,” explains Dr. S. Thomas Carmichael, professor and chair of Neurology at UCLA’s David Geffen School of Medicine. “In other words, the cell-to-cell interaction is disturbed in a toxic way in vascular dementia.”

Mapping the Brain’s Communication Breakdown

The research team tackled a fundamental question: why does brain damage in vascular dementia spread beyond the initial injury sites? To find answers, they mapped the complete “interactome”—all the molecular signals exchanged between different brain cells in both laboratory models and human brain tissue from dementia patients.

This comprehensive analysis revealed a critical communication pathway between blood vessel cells and microglia, the brain’s immune cells. The researchers discovered that two key components of this system—the enzyme CD39 and the adenosine A3 receptor (A3AR)—become severely downregulated in vascular dementia.

A crucial detail not emphasized in the press release: The downregulation occurs through a “synergistic” effect of both aging and blood vessel damage, meaning the combination creates more severe disruption than either factor alone. This explains why vascular dementia predominantly affects older adults and worsens over time.

The Inflammatory Cascade

Under normal conditions, CD39 helps generate adenosine, a molecule that binds to A3AR receptors and moderates inflammation, reducing its harmful effects. When this system fails in vascular dementia, inflammation spirals out of control, creating a toxic environment that damages healthy brain tissue adjacent to initial injury sites.

The discovery provided a clear therapeutic target. The team tested a drug currently in clinical trials for psoriasis, reasoning that if they could restore the anti-inflammatory signaling, they might halt damage expansion and promote brain repair.

Promising Treatment Results

The experimental treatment yielded encouraging results in mouse models of vascular dementia:

• Promoted repair of damaged brain tissue
• Restored memory function
• Improved gait and movement
• Worked even when treatment was delayed, mimicking real-world late diagnosis scenarios

“The most exciting finding was that delayed intervention still worked,” notes lead author Dr. Min Tian, a postdoctoral scholar at UCLA Health. “This is crucial because vascular dementia is often diagnosed late. By targeting the crosstalk between blood vessels and brain cells, we’re addressing the root cause of damage, not just masking symptoms.”

A Different Approach

The research represents a shift from symptom management to addressing underlying disease mechanisms. Rather than trying to prevent initial brain damage, the approach focuses on stopping its expansion and promoting repair of existing injuries.

This strategy could prove particularly valuable for vascular dementia, where damage often occurs through multiple small strokes or chronic blood vessel problems that accumulate over time. By interrupting the inflammatory cascade that spreads damage, the treatment could potentially preserve more brain function.

Next Steps

While the results offer hope for patients and families facing vascular dementia, significant work remains before human trials can begin. The team is now optimizing drug dosing and developing biomarkers to monitor treatment effectiveness.

The research also opens possibilities for treating mixed dementia, where vascular and Alzheimer’s pathology combine. As the leading cause of dementia worldwide, mixed dementia represents an enormous unmet medical need that could benefit from therapies targeting both disease processes.

For the millions affected by vascular dementia and their caregivers, this research offers something that has been elusive: evidence that brain repair is possible and a clear path toward developing treatments that could meaningfully improve outcomes.