- Researchers have discovered a new way that brain blood flow problems are connected to a particular type of dementia called vascular dementia.
- They found that a protein called Piezo1 stops working properly due to the loss of a certain fat (PIP₂).
- Fixing this, they found, can help restore normal blood flow in early tests, which could become a new treatment for dementia.
Vascular dementia is a type of dementia that causes changes in memory, thinking, and behavior that result from conditions that affect the blood vessels in the brain. A person’s cognition and brain function can be greatly affected by the size, location, and number of vascular changes. It can occur alone or be part of a diagnosis of Alzheimer’s disease or other forms of dementia.
A recent study published in Proceedings of the National Academy of Sciences provided insights into the biological mechanisms that regulate blood flow in the brain and suggested a possible therapeutic strategy to correct vascular dysfunction.
These preclinical findings showed that adding a missing phospholipid (fat) back into the bloodstream might help improve blood flow and reduce the symptoms of dementia.
Osama Harraz, PhD, researcher on the study and Bloomfield Professor in Cardiovascular Research, assistant professor of pharmacology at the Larner College of Medicine at the University of Vermont, explained their findings to Medical News Today:
“Our findings highlight a previously unknown, targetable mechanism that links impaired brain blood flow to dementia. We identified dysregulation of a protein (Piezo1) in the brain vasculature as a common feature across conditions associated with reduced brain blood flow. Importantly, we show that this dysfunction is driven by loss of a specific regulatory pathway involving a phospholipid (PIP₂), and that restoring this regulation can reverse blood-flow abnormalities in preclinical models.”
Why these findings are important
“These results shift attention toward neurovascular mechanisms as critical drivers of cognitive decline, rather than passive consequences of neurodegeneration. From a therapeutic standpoint, we suggest that normalizing vascular signaling could represent a new strategy to prevent or slow dementia progression, particularly in forms where vascular dysfunction plays a prominent role.”
— Osama Harraz, PhD
As of 2020, there were over 55 million people worldwide living with dementia. This number is estimated to nearly double over the next 20 years, reaching 78 million by 2030 and 139 million by 2050.
Dementia research often focuses on the role of:
- proteins
- inflammation
- neural activity
- brain cell dysfunction
This study, however, focused on:
- control of cerebral blood flow
- vascular signaling
- role of Piezo1, a protein that lives on the membranes of cells lining the blood vessels
The research findings show how Piezo1 affects cerebral blood flow. It also shows that diseases such as Alzheimer’s disease are linked to increased vascular Piezo1 activity.
The team investigated a phospholipid in the brain cell membranes, PIP2. PIP2 is crucial for regulating ion channels and cell signaling. This is a complex process in which cells control the opening and closing of protein pores. They found that PIP2 is a natural inhibitor of Piezo1.
For example, when PIP2 levels drop, Piezo1 becomes overactive. This disturbs the blood flow in the brain.
They tested adding PIP2 back into the system. This suppressed the Piezo1 activity and restored normal blood flow. This suggests that boosting PIP2 could potentially become a treatment strategy to restore new blood flow and enhance brain function.
“It is important to emphasize that dementia is a multifactorial disorder, and we do not view Piezo1 dysregulation as a single cause. Rather, we believe it represents a contributing factor that interacts with other pathological processes, including inflammation and neurodegeneration.”
— Osama Harraz, PhD
Currently, there is no proven approach to prevent dementia. However, there are certain factors that people can change to help reduce their risk.
For example, there is some encouraging yet inconclusive evidence for three types of behavior changes:
- physical activity
- blood pressure control
- cognitive training
These interventions are encouraging enough that researchers will continue to explore them to determine whether they can truly prevent dementia.
This new study suggests that there may be hope for the future in treating dementia and preventing disease progression.
Dung Trinh, MD, internist of MemorialCare Medical Group in Irvine, CA, and Chief Medical Officer of Healthy Brain Clinic, who was not involved in the study, told MNT, “These findings point to a new therapeutic direction that focuses on restoring brain blood flow, rather than targeting amyloid or tau directly.”
“The study suggests that dysfunction in the brain’s blood vessels—specifically impaired mechanosensing by endothelial cells—may be an upstream contributor to cognitive decline,” he continued.
“If this mechanism holds true in humans, future treatments could aim to normalize neurovascular function earlier in the disease process, potentially slowing or preventing downstream neurodegeneration. Importantly, this approach could complement existing disease-modifying therapies by improving the brain’s resilience, oxygen delivery, and metabolic support—factors that are critical for maintaining cognitive function over time.”
— Dung Trinh, MD
Could vascular health be driving dementia?
“From a prevention standpoint, it raises the possibility that vascular health at the microvascular and cellular level is not just a risk factor, but a modifiable driver of dementia,” Trinh said.
However, he also pointed out that “ it’s essential to emphasize that these results are preclinical. While the mechanism is compelling, translation to human disease will require careful validation, particularly to determine whether similar vascular dysfunction occurs early enough—and broadly enough—to be therapeutically meaningful.”
Findings still ‘preclinical’
“Another key point is that our study demonstrates reversibility. Even in models with established blood-flow deficits, restoring proper regulation of Piezo1 significantly improved cerebral perfusion. This suggests that vascular dysfunction may remain therapeutically tractable beyond the earliest stages of disease. Finally, while these findings are preclinical, they reinforce a growing body of evidence that protecting and restoring brain vascular health is critical for maintaining cognitive function, and that targeting the neurovascular unit may offer new hope for combating dementia and related disorders.”
— Osama Harraz, PhD
This study may open the doors for various aspects of future research.
Trinh noted that the results of this study may accelerate a shift toward vascular-centric and neurovascular coupling research in dementia. He added that future research may:
- Investigate blood-brain flow regulation as an early biomarker of cognitive decline
- Explore mechanosensitive ion channels and lipid signaling as therapeutic targets
- Re-examine dementia models to better integrate vascular dysfunction alongside amyloid, tau, and inflammation
“Our findings support the idea that distinct dementias may share common neurovascular mechanisms, including Alzheimer’s disease and cerebral small vessel disease. This raises the possibility of identifying unified, mechanism-based therapeutic targets rather than disease-specific interventions,” Harraz told MNT.
“Future studies will explore how this pathway interacts with inflammation, neurodegeneration, and genetic risk, as well as whether similar regulatory failures occur in human disease,” he added.
