Scientists discover brain repair targets for vascular dementia

UCLA researchers have identified a key mechanism that drives brain damage in vascular dementia and demonstrated that targeting it with reused drugs can promote brain repair and memory recovery in mice.

The study, published in cells, reveals how inflammation between blood vessels and brain cells creates a toxic cycle, amplifying dementia damage and how the interruption of the process leads to the first effective treatment of the disease studied.

Vascular dementia affects millions of causes of dementia around the world, often happening with Alzheimer’s disease in what doctors call “mixed dementia.” Unlike Alzheimer’s, there is no drug that slows down its progression or promotes the recovery of brain damage caused.

“We think that cells in brain regions where the disease expands will lose normal signals to each other,” explains S. Thomas Carmichael, Ph.D., professor and chair of neurology at UCLA. “In other words, cell-to-cell interactions are disturbed in venous dementia in venous dementia.”

Mapping the communication failure of the brain

The research team solved a basic question: Why do brain damage in vascular dementia spread outside the initial injured site? To find out, they mapped the complete “Interactome” – a molecular signal that all molecular signals exchanged in laboratory models and in human brain tissue in dementia patients.

This comprehensive analysis reveals key communication pathways between vascular cells and microglia (immune cells of the brain). The researchers found that two key components of the system – the enzyme CD39 and adenosine A3 receptor (A3AR) – were severely downregulated in vascular dementia.

Key details not highlighted in the press release: downregulation occurs through the “synergy” effect of aging and vascular damage, meaning that the combination produces more severe damage than any factor alone. This explains why vascular dementia mainly affects older people and worsens over time.

Inflammation cascade

Under normal conditions, CD39 helps produce adenosine, a molecule that binds to the A3AR receptor and relieves inflammation, thereby reducing its harmful effects. When the system fails in vascular dementia, inflammation gets out of control, creating a toxic environment that can damage healthy brain tissue adjacent to the site of the initial injury.

The discovery provides a clear therapeutic target. The team tested a drug in a clinical trial of psoriasis that they might stop dilation and promote brain repair if they can restore anti-inflammatory signaling.

Promising treatment outcomes

Experimental treatments yielded encouraging results in mouse models of vascular dementia:

• Promotes the repair of damaged brain tissue
• Restore memory function
• Gait and exercise improvement
• Even delayed treatment can mimic the late diagnosis in the real world

“The most exciting finding is that delayed interventions are still effective,” noted UCLA Health postdoctoral scholar Min Tian. “This is crucial because vascular dementia is often diagnosed. Targeting crosstalk between blood vessels and brain cells, we are addressing the root cause of the damage, not just masking the symptoms.”

Another way

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

This strategy may prove particularly valuable for vascular dementia, where damage usually occurs through multiple small strokes or chronic vascular problems accumulated over time. By interrupting the inflammatory cascade of diffusion impairment, this treatment may retain more brain function.

Next step

While the results offer hope for patients and families facing vascular dementia, there is still a lot of work to be done before human trials begin. The team is now optimizing drug dosage and developing biomarkers to monitor therapeutic effects.

The study also opens up possibilities for the treatment of mixed dementia, where the pathology of blood vessels and Alzheimer’s disease are combined. As a leading cause of dementia around the world, hybrid dementia represents a huge unmet medical need that can benefit from treatments targeting both disease processes.

For millions of people affected by vascular dementia and its caregivers, the study offers something elusive: Evidence shows that brain repair is possible and a clear pathway to developing treatments that can meaningfully improve outcomes.

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